Research Models

Alzheimer's Disease

There is a large ongoing effort to characterize animal models of AD in order to better understand disease pathophysiology as well as to identify models suitable for investigating potential therapeutics. By organizing information about the characterization of selected AD models, this resource conveys what is known about each one and facilitates comparison between them.

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234 Models
177 Visualizations

Mouse Models (215)
	Name	Other Names	Strain Name	Genetic Background	Gene	Mutation	Modification Info	Modification	Disease	Neuropathology	Behavior/Cognition	Other Phenotype	Availability	Primary Paper	Visualization
	3xTg	<p>-</p>, <p>3xTg-AD</p>, <p>The LaFerla mouse</p>	B6;129-Psen1^tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax	C7BL/6;129X1/SvJ;129S1/Sv	Psen1, APP, MAPT	APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V	Single-cell embryos from mice with knock-in of PSEN1 with the PS1M146V mutation were injected with two human transgenes (APP with the Swedish mutation and MAPT with the P30IL mutation). Transgenes integrated at a single locus under the control of the mouse Thy1.2 promoter.	Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic	Alzheimer's Disease	Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles.	Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task.		The Jackson Lab; available through the JAX MMRRC Stock# 034830; Live	Oddo et al., 2003	Yes
	5xFAD (B6SJL)	<p>-</p>, <p>5XFAD</p>, <p>APP/PS1</p>, <p>Tg6799</p>, <p>Tg-5xFAD</p>	B6SJL-Tg(APPSwFlLon,PSEN1M146LL286V)6799Vas/Mmjax	C57BL/6 x SJL	APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Two transgenes: mutant human APP with the APP Swedish, Florida, and London mutations and containing the 5' untranslated region driven by the mouse Thy1 promoter; and mutant human PSEN1 including the M146L and L286V mutations driven by the mouse Thy1 promoter.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles.	Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype.		The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live.	Oakley et al., 2006	Yes
	5xFAD (C57BL6)	<p>-</p>, <p>5XFAD</p>, <p>APP/PS1</p>, <p>Tg6799</p>, <p>Tg-5xFAD</p>	B6.Cg-Tg(APPSwFlLon,PSEN1M146LL286V)6799Vas/Mmjax	C57BL6	APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Two transgenes: mutant human APP with the APP Swedish, Florida, and London mutations and containing the 5' untranslated region driven by the mouse Thy1 promoter; and mutant human PSEN1 including the M146L and L286V mutations driven by the mouse Thy1 promoter.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer V.	Age-dependent memory deficits, motor phenotype, and reduced anxiety.	The parental origin of the transgenes has been shown to influence plaque burdens in 5xFAD mice on a C57BL6 background—with plaque burdens higher in mice who inherited the APP and PSEN1 transgenes from their fathers, compared with those who inherited the transgenes from their mothers.	Available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Research with this model is available from Scantox Neuro.	Jawhar et al., 2012, Richard et al., 2015	Yes
	A7 APP transgenic			C57BL/6J	APP	APP K670_M671delinsNL (Swedish), APP T714I (Austrian)	Transgene-expressing mutant APP with the Swedish mutation (K670N/M671L) and the Austrian mutation (T714I) under the control of the Thy1.2 promoter.	APP: Transgenic	Alzheimer's Disease	Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months.	Unknown.	Optogenetic stimulation induced epileptic seizures.	Unknown	Yamada et al., 2009	Yes
	AAV-sTREM2 5xFAD	<p>-</p>, <p>5xFAD-sTREM2</p>		5xFAD (C57BL6)	TREM2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Adeno-associated viruses (AAV2/8) expressing EGFP- and FLAG-tagged human TREM2 (amino acids 1-171) under the control of the CAG promoter were injected bilaterally into the lateral ventricles of neonatal 5xFAD mice.	TREM2: Virus; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	AAV-mediated over expression of sTREM2 decreased amyloid plaque burdens and increased numbers of plaque-associated microglia in the brains of 5xFAD mice.	5xFAD mice show impaired learning and memory in the Morris water maze, but AAV-sTREM2 5xFAD mice performed as well as non-transgenic controls.	Long-term potentiation at Shaeffer collateral-CA1 synapses is impaired in 5xFAD mice. AAV-mediated over expression of sTREM2 rescued LTP in AAV-sTREM2 5xFAD mice.	5xFAD mice are available from The Jackson Laboratory, JAX MMRRC Stock# 034848. Research with 5xFAD is available from Scantox Neuro.	Zhong et al., 2019	Yes
	AAV-sTREM2 PS19	<p>-</p>, <p>AAV-sTREM2 Tau P301S</p>		Tau P301S (Line PS19)	TREM2, MAPT	MAPT P301S	Adeno-associated viruses (AAV2/8) expressing EGFP- and FLAG-tagged human TREM2 (amino acids 1-171) under the control of the CAG promoter were injected bilaterally into the hippocampi of 3-month-old male PS19 mice. Control mice received injections of AAV expressing only EGFP.	TREM2: Virus; MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.	AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze.	Levels of p-tau202 and p-tau396 and activity of GSK3β were lower in AAV-sTREM2 PS19 mice compared with PS19 mice who received control vector.	PS19 mice are available from The Jackson Lab: Stock# 008169; Live. Research with PS19 mice is available from Scantox Neuro.	Zhang et al., 2023	Yes
	Abca7A1527G/APOE4/Trem2R47H		B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj}Abca7^em#2AdiujTrem2^em1Adiuj/J	C57BL/6J	Abca7, APOE, Trem2	TREM2 R47H	CRISPR/Cas9 was used to introduce the rs3752246 SNP mutation (p.A1527G) into the Abca7 gene of double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}Trem2^em1Adiuj/J, The Jackson Laboratory Stock# 028709).	Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 030283. Cryopreserved.	The Jackson Laboratory	Yes
	Abca7 KO/APOE4/Trem2*R47H		B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj}Abca7^em#1AdiujTrem2^em1Adiuj/J	C57BL/6J	Abca7, APOE, Trem2	TREM2 R47H	CRISPR/cas9 was used to generate a knock-out mutation of the Abca7 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}Trem2^em1Adiuj/J, The Jackson Laboratory Stock# 028709).	Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 030320. Cryopreserved.	The Jackson Laboratory	Yes
	ADanPP	<p>-</p>, <p>Dan-amyloid</p>, <p>BRI2-Danish</p>, <p>ADan precursor protein</p>	Tg(Prnp-ITM2B)6Jckr and Tg(Prnp-ITM2B)7Jckr	C57BL/6J	ITM2B (BRI2)	BRI2: Familial Danish Dementia (FDD) duplication	Transgenic mice with human BRI2 gene containing the Familial Danish Dementia (FDD) mutation under the control of the Syrian hamster prion protein promoter. The FDD mutation is a 10-nucleotide duplication in the region of the stop codon in the BRI2 gene, resulting in a C-terminally elongated protein.	ITM2B (BRI2): Transgenic	Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy	ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present.	Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype.	Adult mice fail to gain weight with age. Alopecia. Kyphosis.	Available through Mathias Jucker	Coomaraswamy et al., 2010	Yes
	AD-BXD	<p>-</p>, <p>5xFAD BxD</p>	(B6.Cg-Tg(APPSwFlLon,PSEN1M146LL286V)6799Vas/Mmjax x BXD[strain number]	C57BL/6J X BXD[strain number]	APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	“AD-BXD” refers to a panel of transgenic mouse strains, created by crossing 5XFAD mice to members of the BXD genetic reference panel. 5XFAD mice carry APP (with the Swedish, Florida, and London mutations) and PSEN1 (with M146L and L286V mutations) transgenes. The BXD genetic reference panel is a set of recombinant inbred mouse strains derived from crossing the C57BL/6J and DBA/2J inbred strains.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, although the extent of plaque deposition is strain-dependent.	Transgenic AD-BXD mice exhibit cognitive deficits, assessed using contextual fear conditioning. The age of onset and severity of impairment are strain-dependent.		Individual AD-BXD strains are available as F1 hybrids from The Jackson Laboratory (each strain has its own stock number).	Neuner et al., 2019	Yes
	APLP2 Knock-out	<p>-</p>, <p>Amyloid β (A4) precursor-like protein 2 knock-out</p>, <p>APLP2 KO</p>	B6.129S7-Aplp2^tm1Dbo/J	129S7,C57BL/6J; backcrossed to C57BL/6J	Aplp2		Inactivation of the mouse APLP2 gene by deleting a 1.1kb region containing the promoter and exon 1 using a targeting vector containing a PGK-neomycin expression cassette for positive selection and a MC1-TK cassette for negative selection.	Aplp2: Knock-Out	Alzheimer's Disease	Not observed.	Not observed.	Homozygous animals are viable, normal in size, fertile, and do not display any gross physical or behavioral abnormalities up to 22 months of age. No impairments in axonal outgrowth of olfactory neurons following bulbectomy.	The Jackson Lab: Stock# 004142; Cryopreserved	von Koch et al., 1997	No
	APOE2 Knock-In	APOE2 KI		C57BL/6; 129P2, backcrossed to C57BL/6J	APOE		The human APOE2 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated.	APOE: Knock-In	Alzheimer's Disease, Traumatic Brain Injury	Unknown.	Unknown.	2-fold higher level of steady state APOE in brain and higher APOE in serum compared with APOE3 and APOE4 KI animals. Highest levels of serum cholesterol and triglycerides after a 6hr fast.	No longer available through Bruce Lamb	Mann et al., 2004	No
	APOE2 Knock-In, floxed (CureAlz)	<p>-</p>, <p>E2F</p>		C57BL/6J	APOE		The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε2 allele) sequence, flanked by loxP sites.	APOE: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		Available through a material transfer agreement with the Cure Alzheimer’s Fund.	Huynh et al., 2019	Yes
	APOE2 Knock-In (JAX)	<p>-</p>, <p>APOE2 KI</p>, <p>APOE*2 KI</p>	B6.Cg-Apoe^{em3(APOE*)Adiu}j/J	C57BL/6J	APOE		APOE2 KI mice were generated by using CRISPR/Cas9 to introduce two point mutations (leading to arginine to cysteine substitutions at amino acids 130 and 176) in an existing humanized APOE4 knock-in allele (The Jackson Laboratory Stock# 027894).	APOE: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 029017. Live.	The Jackson Laboratory	No
	APOE2 Targeted Replacement	<p>-</p>, <p>APOE2 Humanized Knock-in</p>	B6.129P2-Apoe^{tm1(APOE*2)Mae} N9	129 x C57BL/6; back-crossed to C57BL/6	APOE	APOE R176C (ApoE2)	Targeted gene replacement of the endogenous murine APOE gene with the human APOE2 allele. Targeting construct included exons 2-4 of APOE2.	APOE: Knock-In	Alzheimer's Disease, Multiple Conditions	None reported. White-matter integrity, as assessed by fractional anisotropy, was reported to be higher in the hippocampus and caudate putamen of year-old female APOE2 mice, compared with APOE3 females; these genotype differences were not seen in males.	Findings are mixed, with some studies reporting that APOE genotype—in some cases, interacting with sex or age—affects performance in behavioral assays.	Characteristics of type III hyperlipoproteinemia. Plasma cholesterol and triglyceride levels 2-3x higher than APOE3 mice. Impaired clearance of very-low-density lipoprotein (VLDL) particles. Atherosclerotic plaques. Compared with APOE3 mice, APOE2 mice exhibited higher levels of glucose uptake in the cortex and hippocampus and up-regulation of genes involved in glucose utilization.	Taconic: Stock# 1547-F and 1547-M	Sullivan et al., 1998	No
	APOE3 Knock-In, floxed (CureAlz)	<p>-</p>, <p>E3F</p>		C57BL/6J	APOE		The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε3 allele) sequence, flanked by loxP sites.	APOE: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		Available through a material transfer agreement with the Cure Alzheimer’s Fund.	Huynh et al., 2019	Yes
	APOE3 Knock-In (JAX)	<p>-</p>, <p>APOE3 KI</p>, <p>APOE*3 KI</p>	B6.Cg-Apoe^{em2(APOE*)Adiuj}/J	C57BL/6J	APOE		CRISPR/Cas9 used to introduce a point mutation (leading to an arginine-to-cysteine substitution at amino acid 130) into an existing humanized APOE4 knock-in allele.	APOE: Knock-In	Alzheimer's Disease	APOE3/3 homozygotes are most frequently used as the reference strain for comparisons with other APOE genotypes.	APOE3/3 homozygotes are most frequently used as the reference strain for comparisons with other APOE genotypes.	APOE3/3 homozygotes are most frequently used as the reference strain for comparisons with other APOE genotypes.	The Jackson Laboratory, Stock # 029018; Live	Foley et al., 2022, Sepulveda et al., 2022	No
	APOE3 Knock-In (Lamb)	<p>-</p>, <p>APOE3 KI</p>		C57BL/6; 129P2, backcrossed to C57BL/6J	APOE		The human APOE3 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated.	APOE: Knock-In	Alzheimer's Disease, Traumatic Brain Injury	Unknown.	Unknown.	Intermediate brain APOE and serum cholesterol levels compared with mice with knock-in of APOE4 or APOE2.	No longer available through Bruce Lamb	Mann et al., 2004	Yes
	APOE3 Targeted Replacement	<p>-</p>, <p>APOE3 Humanized Knock-in</p>	B6.129P2-Apoe^{tm2(APOE*3)Mae} N8	129 x C57BL/6; back-crossed to C57BL/6	APOE		Targeted replacement of the endogenous mouse APOE gene with the human APOE3 allele. Targeting vector contained exons 2-4 of human APOE3.	APOE: Knock-In	Alzheimer's Disease, Multiple Conditions	None reported. APOE3 was considered the neutral allele against which the other human APOE genotypes were compared in most studies of neurological phenotypes in Targeted Replacement mice. Data comparing Targeted Replacement mice to wild-type mice are limited.	Findings are mixed, with some studies reporting that APOE genotype—in some cases, interacting with sex or age—affects performance in behavioral assays.	On a standard diet, homozygous mice have normal cholesterol and triglyceride levels, but are more susceptible than wild-type animals to diet-induced atherosclerosis. Data comparing neurological phenotypes in Targeted Replacement mice to wild-type mice are sparse, but APOE3 mice resemble wild-type mice with respect to aspects of hippocampal anatomy and physiology, including LTP and neurogenesis.	Taconic: Stock# 1548-F and 1548-M	Sullivan et al., 1997	No
	APOE4 Knock-In, floxed (CureAlz)	<p>-</p>, <p>E4F</p>		C57BL/6J	APOE		The coding region of the mouse Apoe gene, from the translation initiation codon in exon 2 to the termination codon in exon 4, was replaced with the corresponding human APOE (ε4 allele) sequence, flanked by loxP sites.	APOE: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		Available through a material transfer agreement with the Cure Alzheimer’s Fund.	Huynh et al., 2019	Yes
	APOE4 Knock-In (JAX)	<p>-</p>, <p>APOE4 KI</p>, <p>APOE*4 KI</p>	B6(SJL)-ApoE^{tm1.1(APOE*4)Adiuj}/J	C57BL/6J	APOE		Mouse Apoe exons 2, 3, and most of exon 4 replaced with human APOE sequence including exons 2, 3, 4 and a portion of the 3' UTR sequence.	APOE: Knock-In	Alzheimer's Disease	Possible synapse loss on pyramidal neurons of the medial entorhinal cortex at 6 months of age, compared with APOE3 knock-in mice.	APOE4 knock-in mice did not differ from C57BL/6J controls in tests of locomotor activity, motor coordination, or working memory administered at 2 or 12 months. Nor did E4 carriers differ from APOE3 knock-in mice in tests of spatial learning and memory, activity, exploratory behavior, and anxiety administered at 6 months or in the open field or novel object recognition tests given at 23 months.	Levels of total cholesterol, HDL and LDL decreased in the sera of APOE4 knock-In mice through 14 months, compared with C57BL/6J controls. However, plasma cholesterol, HDL and LDL did not differ between APOE3 and APOE4 knock-in mice through 12 months of age. Increased glucose metabolism and decreased fatty-acid metabolism in the hippocampi of APOE4 knock-ins, compared with APOE3.	The Jackson Laboratory, Stock # 027894; Live	Foley et al., 2022, Sepulveda et al., 2022	No
	APOE4 Knock-In (Lamb)	APOE4 KI		C57BL/6; 129P2, backcrossed to C57BL/6J	APOE		The human APOE4 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated.	APOE: Knock-In	Alzheimer's Disease, Traumatic Brain Injury	Unknown.	Unknown.	Human ApoE is detectable in serum and astrocytes. Compared to mice with knock-in of APOE2 or APOE3, APOE4 mice had the lowest serum cholesterol after a 6 hour fast.	No longer available through Bruce Lamb	Mann et al., 2004	No
	APOE4 Targeted Replacement	<p>-</p>, <p>APOE4 Humanized Knock-in</p>	B6.129P2-Apoe^{tm3(APOE*4)Mae} N8	129 x C57BL/6, back-crossed to C57BL/6	APOE	APOE C130R (ApoE4)	Targeted replacement of the endogenous murine APOE gene with the human APOE4 allele; targeting construct contained exons 2–4 of APOE4.	APOE: Knock-In	Alzheimer's Disease, Multiple Conditions	Mice do not develop amyloid plaques or neurofibrillary tangles. Genotype-dependent differences in brain structure have been reported, but findings are mixed. While some groups have found smaller hippocampal volumes, enlarged ventricles, and compromised white matter in APOE4 mice compared with APOE3, others did not observe these differences.	Findings are mixed, with some studies reporting that APOE genotype—in some cases, interacting with sex or age—affects performance in behavioral assays.	Increased risk of atherosclerosis. Elevated cholesterol, APOE, and APOB-48 on a high fat diet. Transcriptomic and functional evidence for increased aerobic glycolysis and decreased mitochondrial respiration in APOE4 compared with APOE3 mice. Electrophysiological and imaging studies suggest that aged APOE4 mice exhibit neural hyperactivity compared with APOE3 mice in some brain regions.	Taconic: Stock# 1549-F or 1549-M	Knouff et al., 1999	No
	APOE Knock-out	<p>-</p>, <p>APOE KO</p>, <p>APOE -/-</p>, <p>APOE TM1</p>	B6.129P2-Apoe^tm1Unc N11	129 x C57BL/6, back-crossed to C57BL/6	APOE		Inactivation of the endogenous mouse APOE by homologous recombination and insertion of a neomycin cassette.	APOE: Knock-Out	Alzheimer's Disease	Unknown.	Unknown.	Viable; healthy. Undetectable ApoE protein in plasma. Plasma cholesterol 5x higher than wild-type. Artherosclerotic lesions which progress to occlusions of coronary artery by 8 months.	Taconic: Stock# APOE-M and APOE-F	Piedrahita et al., 1992	No
	APP23	<p>-</p>, <p>B6-Tg/Thy1APP23Sdz</p>	B6.Cg-Tg(Thy1-APP)3Somm/J	C57BL/6	APP	APP K670_M671delinsNL (Swedish)	Transgene containing human APP (isoform 751) containing the Swedish (KM670/671NL) mutation under the murine Thy1 promoter.	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages.	Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages.	Hyperactivity observed between the ages of 6 weeks to 6 months. It is not known whether this persists or resolves in older animals. Abnormalities in open field test and impaired performance on rotorod observed from 3 months.	Available through The Jackson Laboratory Stock# 030504, Live	Sturchler-Pierrat et al., 1997	Yes
	APP23 x PS1-R278I		B6.Cg-Tg(Thy1-APP)3Somm/J; Psen1^tm1.1Tcs	C57BL/6J	APP, PSEN1	PSEN1 R278I	This is a cross between APP23 mice, which overexpress APP751 with the Swedish mutation driven by the murine Thy1 promoter, and PSEN1 knock-in mice expressing human PSEN1 with the R278I mutation under the endogenous promoter.	APP: Transgenic; PSEN1: Knock-In	Alzheimer's Disease	Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques.	Short-term memory deficits apparent by 3-4 months as measured by the Y maze.	Reduced γ-secretase activity.	Available through Takaomi Saido	Saito et al., 2011	Yes
	APP751SL/PS1 KI	<p>-</p>, <p>APP(SL)PS1KI</p>, <p>APPxPS1-Ki</p>, <p>APPSL/PS1KI</p>, <p>APP(SL)/PS1(KI)</p>, <p>APP/PS1KI</p>		The PS1KI line was established in 129SV and backcrossed >7 times to C57BL/6 background. The PS1KI were bred with APPSL mice on a C57BL background (two rounds) to obtain a homozygote PS1KI and heterozygote APP.	APP, PSEN1	APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P	This animal is a cross between a PSEN1 knock-in line and an APP over-expressing line. The PS1 knock-in line was generated by introducing two point mutations in the wild-type mouse PSEN1, corresponding to the mutations M233T and L235P. APP751SL overexpresses human APP751 carrying the London (V717I) and Swedish (K670N/M671L) mutations under the control of the Thy1 promoter.	APP: Transgenic; PSEN1: Knock-In	Alzheimer's Disease	Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons.	Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates.	Viable and fertile. 6 month-old animals develop decreases in body weight, and a spinal deformity (kyphosis) is common. Impaired neurogenesis.	Available through Thomas Bayer or Benoit Delatour	Casas et al., 2004	Yes
	APP-C99 (tg13592)	<p>tg13592</p>		C57BL/6 x DBA/2	APP		Transgene consisting of the signal plus 99-amino acid carboxyl-terminal sequence (SbC) of APP under the control of a cytomegalovirus enhancer/β-actin promoter.	APP: Transgenic	Alzheimer's Disease	No neuropathology up to age 29 months; however, pathology reminiscent of inclusion body myopathy observed at 6-12 months: Aβ-immunoreactive deposits in skeletal muscle fibers. Muscle fibers with Aβ-immunoreactive deposits increased with age and also became vacuolated.	Hypoactivity. The acquisition of place learning in the Morris water maze task was impaired.	Higher cytochrome oxidase activity in thalamic nuclei. High levels of Aβ peptides in the plasma.	Available through Ken-ichiro Fukuchi, University of Illinois College of Medicine at Peoria	Fukuchi et al., 1996	No
	APPDutch	<p>-</p>, <p>APP-Dutch</p>, <p>Tg-APP(Dutch)</p>, <p>APP E693Q</p>, <p>APP Dutch</p>	C57BL/6J-Tg(Thy1-APPDutch)#Jckr	C57BL/6J	APP	APP E693Q (Dutch)	Transgenic mice with human APP751 bearing the E693Q mutation under the murine Thy1 promoter.	APP: Transgenic	Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease	Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed.	Unknown.		Available through Mathias Jucker	Herzig et al., 2004	Yes
	APP E693Δ-Tg (Osaka)	<p>Osaka</p>, <p>APP(OSK)-Tg</p>, <p>APP Osaka mutation transgenic</p>, <p>APPOSK-Tg mice</p>, <p>APPOSK mice</p>		B6C3F1, back-crossed to C57Bl/6	APP	APP E693del (Osaka)	Transgenic expression of human APP695 with the Osaka mutation driven by the mouse prion promoter.	APP: Transgenic	Alzheimer's Disease	Age-dependent accumulation of Aβ oligomers within hippocampal and cortical neurons, but negligible deposits of extracellular amyloid. Abnormal tau phosphorylation, but no overt tangle pathology. Synaptic loss and gliosis in hippocampus and cerebral cortex. Late neuronal loss in the CA3 region of the hippocampus.	Memory impairment by eight months as measured by the Morris water maze. Specifically, reduced spatial reference memory in the Morris water maze compared to mice expressing comparable levels of wild-type human APP.		Available from TransGenic Inc.	Tomiyama et al., 2010	Yes
	APP Knock-in	<p>-</p>, <p>APP KI</p>, <p>line ADF</p>	App^tm1Sud/J	Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl<+>; C57BL/6 and maintained on a mixed background	APP	APP K670_M671delinsNL (Swedish), APP V717I (London), APP E693Q (Dutch)	Knock-in of wild-type mouse APP exon 16 (truncated after residue KM), FLAG tag (2 repeats), a stop codon, a poly A signal region from the human growth hormone gene and an additional copy of exon 16 carrying the Swedish mutation and a modified exon 17 with the London and Dutch mutations.	APP: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Lab: Stock# 008390; Cryopreserved	The Jackson Laboratory	No
	App knock-in (humanized Aβ)	<p>-</p>, <p>App<sup>hu/hu</sup></p>	App^em1Bdes	C57BL6J	App		CRISPR/Cas9 was used to introduce the following mutations into the endogenous App gene: G676R (G5R), F681Y (F10Y), R684H (R13H), numbered according to the 770 amino-acid isoform of human APP (position within the Aβ sequence).	App: Knock-In	Alzheimer's Disease	Unknown.	Unknown.	Levels of CTFβ and Aβ are elevated in the brains of these knock-in mice, compared with wild-type animals.	Available through Lutgarde Serneels and The Mary Lyon Centre at MRC Harwell, Archive# HAR:010358.	Serneels et al., 2020	Yes
	APP Knock-out	<p>-</p>, <p>APP null</p>, <p>APP KO</p>	B6.129S7-App^tm1Dbo/J	C57BL/6J	APP		Inactivation of the mouse APP gene by replacing a 3.8 kb sequence encoding the promoter and exon 1 with a neomycin resistance cassette.	APP: Knock-Out	Alzheimer's Disease	Elevated reactive gliosis by 14 weeks in the hippocampus and parts of the neocortex.	Impaired spatial learning as measured by the water maze at 4 and 10 months. Hypoactivity and decreased locomotor activity and forelimb grip strength.	Homozygous knock-out mice weigh 15-20% less than age-matched wild-type mice.	The Jackson Lab: Stock# 004133; Live	Zheng et al., 1995	No
	App KO/APOE4/Trem2*R47H		B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj}App^em2AdiujTrem2^em1Adiuj/J	C57BL/6J	APOE, App, Trem2	TREM2 R47H	CRISPR/Cas9 was used to introduce a 94-bp deletion in exon 14 (APP₆₉₅ numbering) of the App gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (The Jackson Laboratory Stock# 028709).	APOE: Knock-In; App: Knock-Out; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 031722. Cryopreserved.	The Jackson Laboratory	Yes
	APP NL-F Knock-in	<p>-</p>, <p>APP<sup>NL-F/NL-F</sup></p>	App^tm2.1Tcs/App^tm2.1Tcs	C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP I716F (Iberian)	Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and the Swedish and Beyreuther/Iberian mutations.	APP: Knock-In	Alzheimer's Disease	Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.	Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze.	No overexpression of APP. Generates wild-type levels of AICD.	Available through Takaomi Saido	Saito et al., 2014	Yes
	APP NL-G-F Knock-in	<p>-</p>, <p>APP<sup>NL-G-F/NL-G-F</sup></p>, <p>App<sup>NL-G-F</sup></p>	App^tm3.1Tcs/App^tm3.1Tcs	C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic)	Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and three pathogenic mutations (Swedish, Beyreuther/Iberian, and Arctic).	APP: Knock-In	Alzheimer's Disease	Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APP^NL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.	Memory impairment by 6 months as measured by the Y maze.	No overexpression of APP. Wild-type levels of AICD.	Available through Takaomi Saido	Saito et al., 2014	Yes
	AppNL-G-F/MAPT double knock-in	<p>-</p>, <p>App<sup>NL-G-F</sup>/MAPT double knock-in</p>, <p>App<sup>NL-G-F</sup>/MAPT dKI</p>		C57BL/6J	App, MAPT	APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic)	App^NL-G-F mice (mouse App sequence modified to contain a humanized Aβ region and the Swedish, Iberian, and Arctic mutations linked to AD) were crossed with MAPT knock-in mice (entire genomic sequence of murine Mapt, from exon 1 to exon 14, replaced with the human MAPT gene from the ATG codon of exon 1 to the 3'-untranslated region).	App: Knock-In; MAPT: Knock-In	Alzheimer's Disease	Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to App^NL-G-F.	Deficits in the Y-maze test of working memory, similar to App^NL-G-F.	Compared with AppNL-G-F mice, AppNL-G-F/MAPT double knock-in mice showed accelerated propagation of pathological tau species after AD-derived tau was injected into the mouse brain.	Available through Takaomi Saido, RIKEN Center for Brain Science.	Saito et al., 2019, Hashimoto et al., 2019	Yes
	APPPS1	<p>-</p>, <p>APPPS1-21</p>, <p>APP/PS1</p>	B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr	C57BL/6J	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 L166P	Human transgenes APP KM670/671NL and PSEN1 L166P, both under the control of the Thy1 promoter. Integration site is on lower arm of chromosome 2 between 40 and 60 cm.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.	Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months.	Aβ42 concentration in CSF decreases with age, with a 50% reduction by 6 months and an 80% reduction by 18 months. Aβ40 concentration also decreases, but less robustly (45% by 18 months). CSF concentration of total tau increases, starting at 6 months, and reaches a 5-fold increase by 18 months.	Available through Mathias Jucker	Radde et al., 2006	Yes
	APP/PS1/rTg21221	<p>-</p>, <p>APPswe/PSEN1dE9/MAPT</p>, <p>APPswe/PSEN1dE9/CaMKIIa-tTa/TRE-Tg21221</p>		B6.C3 x B6.129 x FVB	APP, PSEN1, MAPT	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APPswe/PSEN1dE9 mice were crossed with B6.129-Tg(CK-tTa) mice where the CaMKIIa promotor drives expression of tetracycline transactivator (tTA) in forebrain neurons. Offsping were then crossed to the Tg21221 line with a responder transgene of wildtype human tau.	APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic	Alzheimer's Disease	Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed.	No data.	N/A	APPswe/PSEN1dE9 mice available through JAX MMRRC Stock# 034829.	Jackson et al., 2016	Yes
	AppSAA Knock-in	<p>-</p>, <p>App<sup>SAA</sup></p>, <p>App<sup>SAA</sup> Knock-in</p>, <p>App<sup>SAA</sup> KI</p>, <p>APP-SAA KI</p>, <p>hAbetaSAA</p>, <p>hAbeta<sup>Swe,Arc,Aus</sup></p>	B6(Cg)-App^tm1.1Dnli/J	C57BL/6J	App	APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP T714I (Austrian)	Homologous recombination was used to humanize the Aβ sequence and introduce the FAD-linked Swedish, Arctic, and Austrian mutations into the murine App gene.	App: Knock-In	Alzheimer's Disease	Homozygotes: Amyloid plaques and plaque-associated microgliosis from 4 months of age; cerebral amyloid angiopathy and dystrophic neurites from 8 months of age. Heterozygotes: Amyloid plaques at 16 months of age.	Unknown.	Increased levels of CSF total tau and neurofilament light chain in AppSAA homozygous mice at 8 months of age. Significant alterations of the transcriptomes and lipidomes in microglia of AppSAA homozygotes.	Available from The Jackson Laboratory Stock# 034711.	Xia et al., 2021	Yes
	APPsw/0; Pdgfrβ+/-	<p>-</p>, <p>Tg2576;Pdgfrβ<sup>+/-</sup></p>		APPsw mice on C57BL/6; Pdgfrβ+/- mice on 129S1/SvlmJ.	APP, PDGFRB	APP K670_M671delinsNL (Swedish)	Progeny of APPsw transgenics (Tg2576) crossed with pericyte-deficient mice. Tg2576 express human APP with the Swedish double mutation driven by the hamster prion promoter. Pericyte-deficient mice were made by disrupting the Pdgfrβ gene using a PGKneobpA expression cassette to replace a 1.8 kb genomic segment spanning the signal peptide to the second immunoglobulin domain of PDGFRβ.	APP: Transgenic; PDGFRB: Knock-Out	Alzheimer's Disease	Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus.	Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition.	Progressive loss of pericytes due to reduced Pdgfrβ signaling. Early and progressive blood brain barrier breakdown, indicated by cerebral accumulation of IgG. Reduced microvascular circulation, indicated by reduced capillary length.	Available through Berislav Zlokovic	Sagare et al., 2013	Yes
	APPSwDI x NOS2 Knock-out	<p>-</p>, <p>APPSwDI/NOS2 bigenic mice</p>, <p>APPSDI/NOS2KO</p>, <p>CVN</p>	B6.Cg-Nos2^tm1LauTg(Thy1-APPSwDutIowa)BWevn/Mmjax	C57BL/6J; C57BL/6N	APP, NOS2	APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa)	APPSwDI x NOS2 knockout animals. APPSwDI transgene expresses APP (isoform 770) with Swedish, Dutch, and Iowa mutations under the control of the mouse Thy1 promoter. NOS2 was disrupted by homologous recombination. The calmodulin binding domain of NOS2 was replaced by the neomycin resistance gene and the reading frame disrupted.	APP: Transgenic; NOS2: Knock-Out	Alzheimer's Disease	Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone.	Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks.	Decreased neuropeptide Y staining throughout the hippocampus, particularly in the CA3 region and subiculum.	The Jackson Lab; available through the JAX MMRRC Stock# 034849; Cryopreserved. Charles River: CVN mouse	Colton et al., 2008, Wilcock et al., 2008	Yes
	APPSwe	<p>-</p>, <p>APPSw</p>, <p>hAPPSwe (line 71)</p>, <p>hAPPSwe (line 72)</p>, <p>huAPPSw</p>	B6.D2-Tg(Thy1-APPSwe)71Blt; B6.D2-Tg(Thy1-APPSwe)72Blt	C57BL/6, DBA/2, crossed to C57BL/6	APP	APP K670_M671delinsNL (Swedish)	Transgene with human APP751 with the Swedish mutation driven by the Thy1.2 promoter.	APP: Transgenic	Alzheimer's Disease	Amyloid plaques by 17-18 months in the neocortex and hippocampus with detection of 5-10 fold more Aβ40 than Aβ42. Plaque burden significantly lower than in the double transgenic PS2APP. Lower levels of insoluble Aβ40 and Aβ42 than the PS2APP mouse at 16-18 months.	Unknown.		Available through Laurence Ozmen	Richards et al., 2003	No
	APP(Swedish) (R1.40)	<p>R1.40</p>, <p>APP<sup>K670/M671</sup></p>, <p>R1.40-YAC</p>	B6.129-Tg(APPSw)40Btla/Mmjax	(129X1/SvJ x 129S1/Sv)F1-Kitl<+>	APP	APP K670_M671delinsNL (Swedish)	A 650 kb YAC transgene containing the entire human APP gene and ~250 kb of flanking sequence was mutated to include the Swedish mutation (K670N/M671L). Founder animals (line R1.40) were backcrossed to C57BL/6J.	APP: Transgenic	Alzheimer's Disease	By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months.	Unknown.	Increased mortality in young homozygous animals, especially females. At 3-4 months mice maintained on the C57BL/6J background exhibit spontaneous seizure-like activity as measured by EEG and are more susceptible to kainic acid-induced seizures.	The Jackson Lab; available through the JAX MMRRC Stock# 034831; Cryopreserved	Lamb et al., 1997	Yes
	APPSwe (line C3-3)	<p>-</p>, <p>APP(695)Swe</p>	C3B6-Tg(APP695)3Dbo/Mmjax	C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J	APP	APP K670_M671delinsNL (Swedish)	Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain and the Swedish mutation under the control of the mouse prion protein promoter.	APP: Transgenic	Alzheimer's Disease	Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age.	Congenic animals showed normal reference and working memory up to 12-14 months.		The Jackson Lab; available through the JAX MMRRC Stock# 034828; Cryopreserved	Borchelt et al., 1996, Savonenko et al., 2003	Yes
	APPSwe (line E1-2)		B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/Mmjax	C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J	APP	APP K670_M671delinsNL (Swedish)	Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain carrying the Swedish mutation under the control of the mouse prion protein promoter.	APP: Transgenic	Alzheimer's Disease	Age-dependent increase in Aβ42, with low levels at 6-14 months and high levels at 24-26 months.	No cognitive impairment in tasks of reference or working memory at 12-14 months.	More than half of the female hemizygous mice do not survive past 15 months of age.	The Jackson Lab; available through the JAX MMRRC Stock# 034835; Cryopreserved	Savonenko et al., 2003, Borchelt et al., 1996	No
	APPSweLon	<p>-</p>, <p>APP YAC Swe/Lon (line J1.96)</p>, <p>B6-J1-96</p>	B6.129S4-Tg(APPSwLon)96Btla/Mmjax	129S4/SvJae-derived J1 ES cells; backcrossed to C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP V717I (London)	A 650 kb YAC transgene containing the entire human APP gene carrying the Swedish and London mutations with ~ 250 kb of flanking sequence; founder animals (line J1.96) have a single copy of the transgene.	APP: Transgenic	Alzheimer's Disease	No amyloid plaques observed at 2 years.	Unknown.		The Jackson Lab; available through the JAX MMRRC Stock# 034837; Cryopreserved	Lamb et al., 1997	No
	APPSwe/PSEN1(A246E)	<p>-</p>, <p>APPSwe (line C3-3)/PSEN1(A246E)(line N-5)</p>, <p>APP/PS1</p>, <p>APPswe + PS1 (A246E)</p>, <p>APP + PS1</p>, <p>AP mouse</p>, <p>C3-3/N-5</p>	B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/Mmjax	Origin: (C57BL/6J x C3H/HeJ)F2	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 A246E	Double transgenic mice; cross of mice expressing human PSEN1 with the A246E mutation driven by the mouse prion protein promoter with mice expressing chimeric APP (isoform 695) with the Swedish mutation driven by the mouse prion promoter. Chimeric APP was created by replacing the mouse Aβ sequence with the cognate human sequence.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus.	Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task.	Increased irritability.	The Jackson Lab: Stock# 003378; Cryopreserved	Borchelt et al., 1997, Borchelt et al., 1996	Yes
	APPSwe/PSEN1dE9 (C3-3 x S-9)	<p>-</p>, <p>APPSwe(line C3-3) X PS1dE9 (line S-9)</p>, <p>C3-3/PS1-dE9</p>, <p>C3-3 x S-9</p>	B6.Cg-Tg(APP695)3Dbo Tg(PSEN1dE9)S9Dbo/J	Line C3-3: C57BL/6J; Line S-9: hybrid strain C3H/HeJ;C57BL/6J) backcrossed to C57BL/6J	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	Double transgenic mice: 1) Line C3-3: mice express a chimeric mouse/human APP gene (isoform 695) carrying the Swedish mutation and 2) Line S-9: mice express a mutant human PSEN1 gene carrying the deletion of exon 9 (dE9) driven by the mouse prion promoter.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers.	Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months.	At 19 months, small but significant decrease in acetylcholinesterase activity in the hippocampus and choline acetyl transferase (ChAT) in the hippocampus and cortex.	The Jackson Lab; available through the JAX MMRRC Stock# 034833; Cryopreserved	Savonenko et al., 2005	Yes
	APPswe/PSEN1dE9 (C57BL6)	<p>-</p>, <p>APP/PS1</p>, <p>C57BL/6J APPswePsen1de9</p>, <p>B6.APB<sup>Tg</sup></p>	B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax	C57BL/6J	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on the original hybrid C57BL/6 x C3H background were backcrossed with C57BL/6J mice.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months. Gliosis and dystrophic neurites are associated with plaques. Amyloid angiopathy has been observed in the retina.	Hyperactivity is apparent by 6 months. Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age.	A substantial proportion of APPswe/PSEN1dE9 mice exhibit electrographic and behavioral seizures.	Available from the Jackson Laboratory, JAX MMRRC Stock# 034832 (formerly Jackson Lab Stock #005864)	Minkeviciene et al., 2008, Minkeviciene et al., 2009	Yes
	APPswe/PSEN1dE9 (line 85)	<p>-</p>, <p>APP/PS1</p>, <p>APPswe/PS1deltaE9</p>, <p>line 85</p>, <p>APP(swe) + PSEN1DeltaE9</p>, <p>APPdE9</p>, <p>Borchelt mice</p>	B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax	C57BL/6;C3H	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	Co-injection of a vector for chimeric mouse/human APP carrying the Swedish mutation and a second for mutant PSEN1 (deltaE9) controlled by independent mouse prion protein promoter elements. The two transgenes co-integrated and co-segragate as a single locus.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity.	Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing).	Kinked tail phenotype that is believed to be due to genetic background.	The Jackson Lab; available through the JAX MMRRC Stock# 034829 (formerly Jackson Lab Stock # 004462); Live	Jankowsky et al., 2001, Jankowsky et al., 2004	Yes
	APPSw-NSE	<p>-</p>, <p>NSE-APPsw</p>		Origin: C57BL/6 x DBA/2	APP	APP K670_M671delinsNL (Swedish)	Transgene containing human APP (isoform 695) bearing the Swedish mutation under the control of neuron specific enolase (NSE) promoter.	APP: Transgenic	Alzheimer's Disease	Increased Aβ42 in the cortex and hippocampus of 12 month old mice, but no plaques. Increased tau phosphorylation and TUNEL-stained nuclei relative to control mice.	In water maze tests, 12 month old mice had longer escape latencies than age-matched control mice.	Metallothionein expression was increased in brain astrocytes and was thought to attenuate Aβ-induced neurotoxicity. Increased Cox-2 and caspase-3 compared to age-matched control mice.	Available through Yong K Kim	Hwang et al., 2004	No
	APP(V642I)KI	Knock-in of APP(V642I)		Origin:C57BL/6 x CBA; chimeric mice breed to CD-1 mice	APP	APP V717I (London)	Targeted knock-in of the V642I mutation into exon 17 of the mouse APP gene using homologous recombination and the Cre-loxP system.	APP: Transgenic	Alzheimer's Disease	Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy.	At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels.		Unknown	Kawasumi et al., 2004	Yes
	APP(V717I)	<p>-</p>, <p>APPlon</p>, <p>APP-london</p>, <p>APPLd</p>, <p>APP-ld</p>, <p>APP(V717I)</p>, <p>APP[V717I]</p>, <p>APP.V717I</p>, <p>APP(London) (line 2)</p>, <p>APP/LD/2</p>	Tg(Thy1-APPLon)2Vln/0	Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N	APP	APP V717I (London)	Transgene containing human APP (isoform 695) with the London mutation driven by the Thy1 promoter.	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.	From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression.	Increased mortality (72% by day 180). Increased incidence of seizures.	Available through the KU Leuven Research and Development Office; the CRO InnoSer offers research services with this line.	Moechars et al., 1999	Yes
	APP(V717I) x PS1(A246E)	<p>-</p>, <p>APPxPS1</p>, <p>APP(V717I)x PS1(A246E)</p>, <p>APP[V717I]x PS1[A246E]</p>, <p>APP.V717I x PS1.A246E</p>	Tg(Thy1-APPLon)2Vln/0; Tg(Thy1-PSEN1*A246E)2Vln/0	Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N	APP, PSEN1	APP V717I (London), PSEN1 A246E	The transgene overexpresses the mutant human amyloid protein precursor APP (isoform 695), which bears the London (V717I) mutation, and human presenilin-1 with the A246E mutation, both under the control of the neuron-specific murine Thy1 promoter.	APP: Multi-transgene; PSEN1: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology.	From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression.		The CRO InnoSer offers research services with this line.	Dewachter et al., 2000	Yes
	Arc48 (APPSw/Ind/Arc)	APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line		Inbred C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic)	A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter.	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20.	At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform.	Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus.	Cryopreserved. Contact Lennart Mucke	Cheng et al., 2004	Yes
	ArcAβ	arcAbeta		Origin: B6D2 F1	APP	APP K670_M671delinsNL (Swedish), APP E693G (Arctic)	Human APP695 transgene containing the Swedish (K670N/M671L) and Arctic mutation (E693G) was generated by site-directed mutagenesis.	APP: Transgenic	Alzheimer's Disease	At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma.	Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze.	Deficits in synaptic plasticity, LTP, and functional connectivity as measured by resting-state fMRI.	Unknown	Knobloch et al., 2007	Yes
	ARTE10		B6;CB-Tg(Thy1-PSEN1M146V/Thy1-APPswe)10Arte	Co-injection of transgenes into B6CBF1 oocytes, back-crossed to C57BL/6	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 M146V	Co-integration of two transgenes, mutant APP carrying the K670N/M671L mutation, and mutant PSEN1 carrying the M146V mutation, both under the control of the Thy-1 promoter.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches.	Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months.	Good breeding capabilities and no premature death.	Taconic: Stock #16347. The CRO InnoSer offers research services with this line.	Willuweit et al., 2009	Yes
	Atg16LΔWD	<p>-</p>, <p>Atg16L<sup>ΔWD</sup></p>, <p>Atg16l1<sup>E230</sup></p>, <p>Atg16L1-WD-deficient</p>, <p>Atg16L1-WD knockout</p>		Mixed 129, C57BL/6	Atg16l1		Two premature stop codons were introduced after the codon for E230, in exon 6 of the Atg16L gene. Mice express a prematurely truncated version of the autophagy protein ATG16L1, missing the WD (tryptophan-aspartate) repeat domain.	Atg16l1: Knock-Out	Alzheimer's Disease	Intracellular and extracellular Aβ deposits, but no dense-core plaques. Microgliosis and neuron loss in 2-year-old mice.	Deficits in the sucrose-preference test, spontaneous alternation in the Y-maze, and novel object recognition test.	Impaired long-term potentiation at CA3-CA1 synapses.	Mice are available from Ulrike Mayer or Thomas Wileman.	Heckmann et al., 2020	Yes
	BACE1 cKO (Hu, Yan) X 5xFAD	<p>-</p>, <p>BACE1<sup>fl/fl/UbcCreER</sup> X 5xFAD</p>		C57BL/6J	Bace1, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	5xFAD mice were crossed with Bace1^fl/flmice (Hu et al., 2018) to generate 5xFAD mice homozygous for a floxed Bace1 gene (“Bace1^fl/fl/5xFAD). Bace1^fl/fl/5xFAD mice were then bred to BACE1 conditional knock-out (Hu, Yan) mice.	Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter.	Normal contextual and cued fear conditioning, tested at 8 to 10 months of age.	Deficit in long-term potentiation at Schaffer collateral–CA1 synapses in slices from 10- to 12-month-old mice, but less severe than that seen in slices from control mice (5xFAD mice homozygous for a floxed Bace1 gene).	Bace1^fl/fl not yet available. UBC-Cre-ERT2 available from The Jackson Laboratory, Stock# 007001. 5xFAD available from The Jackson Laboratory, JAX MMRRC Stock# 034848.	Hu et al., 2018	Yes
	Bace1 conditional knock-out (adult, whole body) (Vassar)	<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>fl/fl</sup>;R26CreER<sup>T2</sup>-TAM</p>		C57BL6	Bace1		Mice in which exon 2 of Bace 1 is flanked by LoxP sites (Ou-Yang et al., 2018) were crossed with R26CreER^T2mice (Ventura et al., 2007), which carry a transgene encoding Cre recombinase fused to the estrogen receptor, inserted at the ROSA26 locus.	Bace1: Conditional Knock-out	Alzheimer's Disease	Defects in axonal organization.	Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations.		BACE1^fl/fl available through Robert Vassar; R26CreER^T2 available through The Jackson Laboratory Stock# 008463, Live	Ou-Yang et al., 2018	Yes
	BACE1 conditional knock-out (Hu, Yan)	<p>-</p>, <p>BACE1 cKO</p>, <p>BACE1<sup>fl/fl/UbcCreER</sup></p>		C57BL/6J	Bace1		These mice were generated by crossing Bace1^fl/fl mice (Hu et al., 2018), in which exon 2 of the mouse Bace1 gene is flanked by loxP sites, with UBC-Cre-ERT2 mice (The Jackson Laboratory, Stock# 007001), which carry a transgene encoding Cre recombinase fused to a modified human estrogen receptor, driven by the ubiquitin C promoter.	Bace1: Conditional Knock-out	Alzheimer's Disease	No gross morphological changes observed.	BACE1-deficient mice and Bace1^fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age.	Impaired long-term potentiation at Schaffer collateral–CA1 synapses in slices obtained from 10- to 12-month-old mice.	Bace1^fl/fl not yet available. UBC-Cre-ERT2 available from The Jackson Laboratory, Stock# 007001.	Hu et al., 2018	Yes
	Bace1 conditional knock-out (neonatal, forebrain) (Vassar)	<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>fl/fl</sup>;CamKIIα-iCre</p>		C57BL6	Bace1		Mice in which exon 2 of Bace1 is flanked by LoxP sites (BACE1^fl/fl) were crossed with mice carrying a transgene encoding Cre recombinase driven by the CamKIIα promoter (Casanova et al., 2001).	Bace1: Conditional Knock-out	Alzheimer's Disease	Hypomyelination and defects in axon organization.	Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments.	Spontaneous behavioral seizures and epileptiform discharges in EEGs.	BACE1^fl/fl available through Robert Vassar; CamKIIα-iCre available through the European Mouse Mutant Archive (EMMA) ID# EM: 01153, cryopreserved, sperm	Ou-Yang et al., 2018	Yes
	Bace1 conditional knockout (Tesco)	<p>-</p>, <p>Bace1 cKO</p>, <p>BACE1<sup>flox/flox</sup>;RosaCreERT2<sup>+/WT</sup></p>	C57BL/6-Bace1^tm1.1mrl	C57BL/6N	Bace1		Mice in which exon 2 of Bace1 is flanked by LoxP sites were crossed with R26-CreERT2 mice, which carry a transgene encoding Cre recombinase fused to the estrogen receptor, inserted at the ROSA26 locus.	Bace1: Conditional Knock-out	Alzheimer's Disease	None observed: hippocampal mossy fiber organization and sciatic-nerve myelination were normal.	Performed similarly to controls in a battery of tests (Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition task).	Deficit in long-term potentiation at Schaffer collateral–CA1 synapses.	BACE1^flox/flox available through Taconic Model# 8263, Cryopreserved. RosaCreERT2 (R26-CreERT2) available through The Jackson Laboratory Stock# 008463, Live.	Lombardo et al., 2019	Yes
	BACE1 Knock-out	<p>-</p>, <p>BACE1<sup>-/-</sup></p>, <p>BACE1 KO</p>	B6.129-Bace1^tm1Pcw/J	C57BL/6J	BACE1		Homologous recombination was used to disrupt a 2kb section of BACE1 containing exon 1 replacing it with a neomycin selection cassette and the HSV thymidine kinse gene.	BACE1: Knock-Out	Alzheimer's Disease	Hypomyelination in the hippocampus and cerebral cortex, but normal axonal development.	Increased thermal pain sensitivity as measured by a hot plate test. Decreased grip strength.	Homozygous mice are viable, fertile, normal in size. No BACE1 protein is detected by Western blot. Primary cultures of cortical neurons do not secrete Aβ1-40/42, Aβ11-40/42 or β-C terminal fragments (β-CTFs).	The Jackson Lab: Stock# 004714; Live	Cai et al., 2001	No
	BACE2 Knock-out	<p>-</p>, <p>BACE2delta6</p>, <p>BACE2 KO</p>	B6;129P2-Bace2^tm1Bdes/J	Strain of origin: 129P2/OlaHsd	BACE2		Cre mediated recombination was used to remove exon 6 of BACE2. A targeting vector containing a loxP site and hygromycin resistance gene flanked by FRT sites was introduced into intron 5 and a second loxP site was inserted within intron 6. Heterozygous mice were crossed with mice expressing Cre under the ubiquitous phosphoglycerate kinase promoter to delete exon 6 in progeny.	BACE2: Knock-Out	Alzheimer's Disease	Not observed.	Not observed.	BACE2 deficient fibroblasts produced higher levels of Aβ compared with wild-type cells.	The Jackson Lab: Stock# 005618; Cryopreserved	Dominguez et al., 2005	No
	BRI-Aβ40 (BRI2-Aβ40)	BRI2-Aβ40	B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J	B6C3, backcrossed to C57BL/6J to generate congenic strain			Construct encodes a fusion protein of the BRI protein and Aβ40 driven by the mouse prion promoter; Aβ40 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ40.	Transgenic	Alzheimer's Disease	No overt amyloid pathology or detergent-insoluble amyloid-β.	Hemizygous mice on a mixed background (C57/B6//C3H) have intact cognition as measured by fear conditioning at 12 and 14-17 months.		The Jackson Lab: Stock# 007180; Cryopreserved	McGowan et al., 2005	No
	BRI-Aβ42 (BRI2-Aβ42)	BRI2-Aβ42, BRI-Abeta42	B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J	B6C3, backcrossed to C57BL/6J to generate congenic strain			Construct encodes a fusion protein of the BRI protein and Aβ42 driven by the mouse prion promoter. Aβ42 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ42.	Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss.	On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.		The Jackson Lab: Stock# 007182; Cryopreserved	McGowan et al., 2005	Yes
	CAST.APP/PS1		CAST.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How	CAST/EiJ	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with CAST/EiJ mice for at least six generations.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in hippocampal area CA1.	Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in males (data from females is not available, as wild-type females are unable to perform this test).		Available from The Jackson Laboratory, Stock #25973.	Onos et al., 2019	Yes
	Ceacam1 KO/APOE4/Trem2*R47H	<p>-</p>, <p>APOE4/Trem2*R47H/Ceacam1 knock-out</p>	B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj}Ceacam1^em#1AdiujTrem2^em1Adiuj/J	C57BL/6J	APOE, Ceacam1, Trem2	TREM2 R47H	CRISPR/cas9 was used to generate a knock-out mutation of the Ceacam1 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}Trem2^em1Adiuj/J, The Jackson Labortory Stock# 028709).	APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 030673. Cryopreserved.	The Jackson Laboratory	Yes
	Clasp2L163P/APOE4/Trem2R47H		B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}Clasp2^em1Adiuj Trem2^em1Adiuj/J	C57BL/6J	Clasp2, APOE, Trem2	TREM2 R47H	CRISPR/cas9 was used to generate a knock-in L163P mutation of the Clasp2 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene.	Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 031944. Cryopreserved.	The Jackson Laboratory	Yes
	CNS-restricted PS1 cKO		fPS1/fPS1Δ;Nestin-Cre (PS1 cKO)	C57BL6/129	PSEN1		PS1 inactivation in neuronal progenitor cells (NPCs) and NPC-derived neurons and glia was achieved by crossing a floxed PS1 mouse with a Nestin-Cre transgenic mice.	PSEN1: Conditional Knock-out	Alzheimer's Disease	Premature differentiation of neural progenitor cells results in reduced cells and neurons. 45 percent of late-born neurons fail to migrate to their appropriate positions in the superficial cortical layers.	Gross behavior deficits.	Mice are small. Premature death at 2-3 months of age.	Available through Jie Shen	Wines-Samuelson et al., 2005	No
	Dp(16)1Yey/+		B6.129S7-Dp(16Lipi-Zbtb21)1Yey/J	C57BL/6J			A 22.9Mb duplication extending from the Lipi gene to the Zbtb21 gene on mouse chromosome 16 was generated in mouse ES cells using Cre/loxP-mediated chromosome engineering. The desired ES cell clones were injected into C57BL/6J-Tyrc-Brd blastocysts to generate chimeric mice, and these were bred to establish the B6.129S7-Dp(16Lipi-Zbtb21)1Yey/J (Dp(16)1Yey/+) mouse strain. The duplicated region includes 115 genes, including App, which are orthologous to human chromosome 21 (Hsa21), covering about 65 percent of the chromosome.	Multi-transgene	Down's Syndrome, Alzheimer's Disease	Neuronal loss in the entorhinal cortex, locus coeruleus, and the basal forebrain magnocellular complex; increased tau pathology and increased astrocyte and microglia levels.	Impairments in contextual memory, spatial learning, novel object recognition memory, and vocalizations.	Altered motor coordination, sleep patterns, hearing, and vocalizations. Also, cardiopulmonary, craniofacial, skeletal, reproductive, immunological, and metabolic anomalies.	Available from The Jackson Lab: Strain 013530.	Li et al., 2007	Yes
	Dp1Tyb		B6.129P2-Dp(16Lipi-Zbtb21)1TybEmcf/J	C57BL/6J			LoxP sites were inserted proximal to the Lipi gene and distal to the Zbtb21 gene in HM-1 ES cells (23Mb duplication covering about 65% of Hsa21). Cre recombinase was transiently expressed in double-targeted ES cells to induce recombination between the loxP sites. Targeted clones were injected into blastocysts to generate chimeric mice and these were bred to establish the model mouse strain by standard methods.	Knock-In	Down's Syndrome, Alzheimer's Disease	No amyloid plaques. At 14 weeks, smaller and rounder brain, reduced medial prefrontal cortex and dorsal hippocampus volumes, reduced density of neurons, and increased density of microglia in the hippocampus. Altered hippocampal metabolites including glutamine and the glutamine/glutamate ratio. Reduced IB4 neurons in the DRG.	Exploratory behavior is impaired at 8 weeks of age. Fear memory is impaired at 10 months. Motor function is impaired at 12-15 weeks of age. Sleep architecture is disrupted at 16-weeks of age. Spatial working memory is impaired at 3-months of age.	Heart, lung, hematologic, skeletal, ear, and metabolic abnormalities; many similar to those associated with Down syndrome.	Available from the Jackson Lab: Strain 037183 and the European Mutant Mouse Archive EM:10557.	Lana-Elola et al., 2016	Yes
	Dp9Tyb		C57BL/6J.129P2-Dp(16Lipi-Hunk)9TybEmcf/TybH	C57BL/6J			In HM-1 ES cells, LoxP sites were inserted proximal to the Lipi gene and distal to the Hunk gene in chromosome 16, the mouse ortholog of human chromosome 21. Cre recombinase was used to induce recombination between the loxP sites and generate a duplicated sequence.		Down's Syndrome, Alzheimer's Disease	Unknown.	No locomotor defects as assessed by Rotarod at 12 weeks of age.	Improved trabecular and cortical bone measurements, no heart defects.	Available from the European Mutant Mouse Archive (EMMA) (strain ID EM:10565).	Lana-Elola et al., 2016	Yes
	E2FAD	<p>-</p>, <p>APOE2-FAD</p>, <p>APOE2 Targeted Replacement x 5xFAD</p>		C57BL/6	APOE, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APOE2 Targeted Replacement mice were crossed with the 5xFAD line.	APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.	In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice.		5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE2 Targeted Replacement mice are available through Taconic, Stock# 1547-F or 1547-M.	Youmans et al., 2012	Yes
	E3FAD	<p>-</p>, <p>APOE3-FAD</p>, <p>APOE3 Targeted Replacement x 5xFAD</p>		C57BL/6	APOE, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APOE3 Targeted Replacement mice were crossed with the 5xFAD line.	APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.	In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice.		5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE3 Targeted Replacement mice are available through Taconic, Stock# 1548-F or 1548-M.	Youmans et al., 2012	Yes
	E4FAD	<p>-</p>, <p>APOE4-FAD</p>, <p>APOE4 Targeted Replacement x 5xFAD</p>		C57BL/6	APOE, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APOE4 Targeted Replacement mice were crossed with the 5xFAD line.	APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.	Age-dependent learning and memory deficits in the Y maze and Morris water maze.		5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE4 Targeted Replacement mice are available through Taconic, Stock# 1549-F or 1549-M.	Youmans et al., 2012	Yes
	GFAP-APOE4/APOE Knock-out	<p>-</p>, <p>APOE4 (line1)/APOE KO</p>, <p>Tg(GFAP-APOE*4)1Hol</p>	B6.Cg-Apoe^tm1Unc Cdh18^{Tg(GFAP-APOE_i4)1Hol}/J. Formerly: B6.Cg-Tg(GFAP-APOE_i4)1Hol Apoetm1Unc/J	B6/CBA; back-crossed onto C57BL6 background	APOE		Transgene of human APOE4 driven by the GFAP promoter; crossed to APOE knock-out mice.	APOE: Transgenic; APOE: Knock-Out	Alzheimer's Disease	Developing and adult mice express human APOE4 in glia and neuropil.	Unknown.	Mice are viable, normal in size, and do not display any gross physical or behavioral abnormalities.	The Jackson Lab: Stock# 004631; Cryopreserved	Sun et al., 1998	No
	hAbeta/APOE4/Trem2*R47H (LOAD2)	<p>LOAD2</p>	B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj}App^em#1AdiujTrem2^em1Adiuj/J	C57BL/6J	APOE, APP, Trem2	TREM2 R47H	CRISPR/Cas9 was used to introduce the G601R, F606Y, and R609H (APP₆₉₅ numbering) point mutations into the App gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}Trem2^em1Adiuj/J, Jackson Lab Stock# 028709).	APOE: Knock-In; APP: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 030670. Live.	The Jackson Laboratory	Yes
	hAbeta-loxP-KI	<p>-</p>, <p>hAbeta-loxP-KI on mixed B6J and B6NJ</p>	B6(SJL)-App^tm1.1Aduci/J	mixed B6J; B6NJ	APP		Three point mutations were introduced into exon 14 (exon numbering according to APP₆₉₅, with 16 exons) of the mouse App gene, to produce three amino acid substitutions within the Aβ sequence (amino acids 5 (G to R), 10 (F to Y) and 13 (R to H) of Aβ). Exon 14 is also flanked by loxP sites.	APP: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		Available February, 2019 from The Jackson Laboratory, Stock# 030898	The Jackson Laboratory	Yes
	hAβ-KI	<p>-</p>, <p>hAbeta-loxP-KI</p>	B6(SJL)-App^tm1.1Aduci/J	mixed C57BL/6J and C57BL/6NJ	App		Homologous recombination was used to humanize the Aβ sequence of the endogenous App gene and to add loxP sites flanking exon 14.	App: Knock-In	Alzheimer's Disease	No amyloid plaques observed through 22 months of age. Accelerated formation of OC-immunoreactive and Periodic Acid Schiff-positive granules.	Differed from wild-type mice in the contextual fear conditioning test by 10 months of age and in the novel object recognition task by 14 months.	Impaired long-term potentiation by 18 months of age. Changes in gene expression that overlap those seen in sporadic AD.	Available from The Jackson Laboratory (JAX Stock No. 030898).	Baglietto-Vargas et al., 2021	Yes
	hBACE			C57B6/C3H	BACE1		Transgene of human BACE1 driven by the prion protein (PrP) promoter.	BACE1: Transgenic	Alzheimer's Disease	No evidence of Aβ deposition in single transgenic animals.	Unknown.		Unknown	Lee et al., 2005	No
	hBACE54			C57BL/6 J	BACE1		Wild-type human BACE driven by the murine Thy1 promoter.	BACE1: Transgenic	Alzheimer's Disease	Not observed.	Unknown.	Decreased levels of full-length mature APP and increased levels of C99 and C89. Human BACE mRNA 4x higher than endogenous murine BACE. Highest expression of human BACE protein in cortex and hippocampus, lowest in cerebellum.	Available through Material Transfer Management at Novartis	Bodendorf et al., 2002	No
	hCR1 KI on APOE4/Trem2		B6(SJL)-Cr2^{tm1(CR2,CR1)How} Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J	C57BL/6J	Cr2, CR1, CR2, APOE, Trem2	TREM2 R47H	This mutant line was generated by crossing APOE4/Trem2*R47H mice to mice in which the endogenous Cr2 gene was replaced with human CR1 and CR2 (The Jackson Laboratory Stock# 027713).	Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 031668. Cryopreserved.	The Jackson Laboratory	Yes
	htau	<p>-</p>, <p>human tau</p>	B6.Cg-Mapt^tm1(EGFP)KltTg(MAPT)8cPdav/J	The targeted allele was created in 129S4/SvJae-derived J1 embryonic stem cells that were subsequently injected into C57BL/6 blastocysts. The transgenic allele was generated in embryos derived from a cross between Swiss Webster and B6D2F1. Mice containing both alleles were back-crossed to C57BL/6 mice .	MAPT		Double mutant mice were generated by mating mice that express human tau (8c mice) (Duff et al., 2000), with tau knockout mice that have a targeted disruption of exon one of tau (Tucker et al., 2001), then back-crossed to obtain mice that are homozygous for disrupted murine MAPT while carrying the human tau transgene.	MAPT: Knock-Out; MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately thioflavin-S positive neurofibrillary tangles. Pathology most severe in neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some neuronal loss.	Normal object-recognition memory and spatial learning/memory (as assessed by the Morris Water Maze) at four months, but impaired at 12 months (Polydoro et al., 2009).	General health, weight, basic reflexes, sensory responses, locomotor function, anxiety level, and gross motor function were not different from age-matched controls (Polydoro et al., 2009).	The Jackson Lab: Stock# 005491; Live. Scantox Neuro offers research services with this line.	Andorfer et al., 2003	Yes
	hTau-A152T	<p>-</p>, <p>CaMKII-tTA/TRE-hTau-A152T</p>	C57BL/6-Tg(tetO-MAPT*A152T)L1Lms/J	C59Bl/6J	MAPT	MAPT A152T	These bigenic mice use the CaMKIIα promoter to drive expression of tetracycline transactivator (tTA) in forebrain neurons. The responder transgene is the 1N4R isoform of human tau with the A152T mutation. Expression is constitutive unless suppressed by doxycycline.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus.	Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal.	Increase in basal synaptic activity and epileptiform spikes. Life span normal.	Available as single transgenics: The Jackson Lab Stock# 028979 (cyropreserved) and Stock# 007004 (live)	Maeda et al., 2016	Yes
	hTau-AT (hTau40-AT)	<p>hTau40-AT</p>, <p>Ala152T-Tau</p>, <p>A152T-Tau</p>, <p>Tau/A152T</p>		C57BL/6	MAPT	MAPT A152T	Human full-length tau (hTau40) isoform 2N4R with the A152T mutation expressed under the Thy1.2 promotor is located in the ROSA26 locus.	MAPT: Knock-In	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses.	Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal.	Increase in basal synaptic transmission.	Available through Eva Mandelkow	Decker et al., 2016, Sydow et al., 2016	Yes
	hTau.P301S	<p>-</p>, <p>Tau.P301S</p>, <p>hTAU[P301S]</p>, <p>tau[P301S]</p>, <p>Tg2541</p>	Thy1-hTau.P301S (CBA.C57BL/6)	CBAxC57BL/6	MAPT	MAPT P301S	Transgenic mice overexpressing a human tau isoform that is 383 amino acids long with four microtubule-binding repeat domains and without N-terminal inserts (4R/0N). Site-directed mutagenesis was used to introduce the P301S mutation. Transgene is under the control of the neuron-specific murine Thy-1 promoter.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis.	Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months.	Muscle weakness, tremor. Frequent eye inflammation.	Available for academic use from Michel Goedert and for commercial use from LifeArc. Also available from The Mary Lyon Centre at MRC Harwell, Archive# HAR: 011664. The CRO InnoSer offers research services with this line.	Allen et al., 2002	Yes
	hTREM2-KI		C57BL/6J-Trem2^{em3(TREM2)Aduci}/J	C57BL/6J	TREM2		Mouse genomic DNA between the start codon in exon 1 and the stop codon in exon 5 of the Trem2 gene was replaced with the corresponding human genomic DNA sequence.	TREM2: Knock-In	Alzheimer's Disease				Register interest. The Jackson Laboratory Stock No. 038103.	The Jackson Laboratory	Yes
	hTREM2-R47H_KI		C57BL/6-Trem2^{em2(TREM2*R47H)Aduci}/J	C57BL/6	TREM2	TREM2 R47H	Mouse genomic DNA between the start codon in exon 1 and the stop codon in exon 5 was replaced by the corresponding human genomic DNA sequence, and the codon at position 47 was changed from CGC (encoding arginine) to CAC (encoding histidine).	TREM2: Knock-In	Alzheimer's Disease				Available for pre-order. The Jackson Laboratory, Stock No. 037497.	The Jackson Laboratory	Yes
	Human-BACE1			C57BL	BACE1		Transgene expressing wild-type human BACE1 driven by the mouse Thy1 promoter.	BACE1: Transgenic	Alzheimer's Disease	Not observed.	Unknown.	Transgene expressed in neurons only. No change in processing of endogenous murine APP.	No longer available through Michael Willem	Willem et al., 2004	No
	Il1rap KO/APOE4/Trem2*R47H		B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj}Il1rap^em#1AdiujTrem2^em1Adiuj/J	C57BL/6J	APOE, Il1rap, Trem2	TREM2 R47H	CRISPR/cas9 was used to generate a knock-out mutation of the Il1rap gene of double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}Trem2^em1Adiuj/J, The Jackson Laboratory Stock# 028709).	APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 030304. Cryopreserved.	The Jackson Laboratory	Yes
	J20 (PDGF-APPSw,Ind)	<p>PDGF-APPSw,Ind</p>, <p>PDGF-hAPP695,751,770V171F, KM670/671NL</p>, <p>hAPPJ20</p>, <p>hAPP</p>, <p>Mucke mice</p>	B6.Cg-Zbtb20^{Tg(PDGFB-APPSwInd)20Lms}/2Mmjax	C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter.	APP: Transgenic	Alzheimer's Disease	Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity.	Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated.	On the C57BL/6J background hippocampal hyperexcitability was observed and cortical and hippocampal spontaneous nonconvulsive seizures.	The Jackson Lab; available through the JAX MMRRC Stock# 034836-JAX; Live	Mucke et al., 2000	Yes
	JNPL3(P301L)	<p>-</p>, <p>TauP301L-JNPL3</p>	Tg(Prnp-MAPT*P301L)JNPL3Hlmc	C57BL/6, DBA/2, SW Mixed Background	MAPT	MAPT P301L	Transgene for human MAPT (4R0N) with the P301L mutation driven by the mouse prion promoter.	MAPT: Transgenic	Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease	Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord.	By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization.	Eye irritiation, possibily due to carrying the Pde6brd1 retinal degeneration mutation carries Pde6brd1 mutation	Taconic: Stock#2508 (homozygote); #1638 (heterozygote and wild-type) has been discontinued.	Lewis et al., 2000	Yes
	Kif21bT82T/APOE4/Trem2R47H		B6(SJL)-Kif21b^em1Adiuj Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J	C57BL/6J	Kif21b, APOE, Trem2	TREM2 R47H	CRISPR/cas9 was used to generate a knock-in T82T mutation of the Kif21b gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene.	Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 031938. Cryopreserved.	The Jackson Laboratory	Yes
	MAPT(H1.0)-GR		B6J.B6N-Tc(HSA17)2Mdk/J	C57BL/6J	MAPT, MAPT-AS1, Mapt		A 190-kb region from human chromosome 17—including MAPT (H1 haplotype), MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1.	MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Unknown.	Unknown.		Available from The Jackson Laboratory, Stock No. 035398.	Benzow et al., 2024	Yes
	MAPT(H2.1)-GR		B6J.B6N-Tc(HSA17)1Mdk/J	C57BL/6J	MAPT, MAPT-AS1, Mapt		A 190-kb region from human chromosome 17—including MAPT (H2 haplotype), MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1.	MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Unknown.	Unknown.		Available from The Jackson Laboratory, Stock No. 033668.	Benzow et al., 2024	Yes
	MAPT knock-in	<p>-</p>, <p>MAPT KI</p>, <p>hTau KI</p>		C57BL/6J	MAPT		Homologous recombination was used to replace the entire genomic sequence of murine Mapt (from exon 1 to exon 14) with the human MAPT gene from the ATG codon of exon 1 to the 3'-untranslated region (H2 haplotype; NCBI Reference Sequence: NG_007398).	MAPT: Knock-In	Alzheimer's Disease, Other Tauopathy	No evidence of increased neuroinflammation, neuronal death, or brain atrophy in MAPT knock-in mice, compared with wild-type mice.	MAPT knock-in mice perform similarly to wild-type mice in the Y-maze test of working memory.	Compared with wild-type mice, MAPT knock-in mice showed accelerated propagation of pathological tau species after AD-derived tau was injected into the mouse brain.	Available through Takaomi Saido, RIKEN Center for Brain Science.	Saito et al., 2019, Hashimoto et al., 2019	Yes
	MthfrC677T/APOE4/Trem2R47H		B6(SJL)-Mthfr^em1Adiuj Apoe^{tm1.1(APOE*4)Adiuj}Trem2^em1Adiuj/J	C57BL/6J	Mthfr, APOE, Trem2	TREM2 R47H	CRISPR/Cas9 was used to introduce the A262V mutation into the Mthfr gene of APOE4/Trem2*R47H mice—double mutant mice with a humanized APOE4 gene and the R47H point mutation knocked into the mouse Trem2 gene.	Mthfr: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 030922. Cryopreserved.	The Jackson Laboratory	Yes
	mThy-1 3R Tau (line 13)	<p>line 13</p>		C57BL/6 x DBA/2F1, crossed with DBA	MAPT	MAPT L266V, MAPT G272V	Transgene expressing human 3R tau bearing the L266V and G272V mutations under the neuronal mThy-1 promoter.	MAPT: Transgenic	Frontotemporal Dementia, Pick's disease, Alzheimer's Disease	Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology.	Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test.	Increased anxiety.	Unknown	Rockenstein et al., 2015	Yes
	mThy1-hAPP751 (TASD41)	<p>TASD41</p>, <p>Line 41</p>, <p>hAPPSL</p>, <p>hAPP-SL</p>, <p>AβPP751</p>, <p>mThy1-hAβPP751 Swe Lon (line 41)</p>, <p>APP751SL</p>, <p>hAPPlon/swe line 41</p>, <p>APP41</p>	mThy1-hAβPP751 Swe Lon	C57BL/6 x DBA	APP	APP K670_M671delinsNL (Swedish), APP V717I (London)	The transgene over-expresses the mutant human amyloid protein precursor (751 isoform), which bears both the Swedish (K670N/M671L) and the London (V717I) mutations, under the control of the murine Thy1 promoter.	APP: Transgenic	Alzheimer's Disease	Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region.	Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration.		Available through Eliezer Masliah. The CRO PsychoGenics offers research services with this line.	Rockenstein et al., 2001	Yes
	NSE-ApoE3			Origin: C57BL/6J; backcrossed with murine APOE-null mice	APOE		ApoE3 minigene driven by the rat neuron-specific enolase promoter.	APOE: Transgenic	Alzheimer's Disease	Human ApoE3 protected against the age-dependent neurodegeneration seen in APOE -/- mice.	Unknown.	Widespread neuronal expression of ApoE in the brain. Expression of ApoE3 protected against kainic acid-induced neuronal damage (loss of synaptophysin-positive presynaptic terminals and MAP2-positive neuronal dendrites in the neocortex and hippocampus, and a disruption of neurofilament-positive axons in the hippocampus).	Available through Robert Mahley	Raber et al., 1998	No
	NSE-ApoE4			Origin: C57BL/6J; backcrossed with murine ApoE-null mice	APOE		The ApoE4 minigene driven by the rat neuron-specific enolase promoter.	APOE: Transgenic	Alzheimer's Disease	Not observed.	NSE-ApoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and seen primarily in females.	Neuronal ApoE expression was widespread in the brain. Expression of ApoE4 did not protect against kainic acid-induced neuronal damage.	Available through Robert Mahley	Raber et al., 1998	No
	NSE-APP751		JU.Tg(NSE-APP751)Cordell	JU (Developed by Eric Bradford at University of California, Davis)	APP		Transgene expresses wild-type human APP751 isoform under the control of the rat neural-specific enolase (NSE) promoter.	APP: Transgenic	Alzheimer's Disease	Age-dependent increase in Aβ deposits and tau immunoreactivity.	Learning and memory deficits are age-dependent as assessed on spontaneous alternation in a Y maze and in the water-maze task.		Extinct	Quon et al., 1991	Yes
	NSE-hPS2(N141I)			C57BL/6× DBA/2	PSEN2	PSEN2 N141I (Volga)	Transgene containing human PSEN2 carrying the N141I mutation driven by the neuron-specific enolase (NSE) promoter.	PSEN2: Transgenic	Alzheimer's Disease	Not observed.	Behavioral deficits in the water maze at 12 months in mice expressing mutatnt as well as wild-type PSEN2, including longer escape latencies than wild-type mice, but no difference in swimming speed.	Expression of PSEN2 was higher in mice expressing mutant as well as wild-type PSEN2 compared to age-matched, non-transgenic mice. Alterations in levels of Aβ42, caspase-3 and Cox-2 proteins.	Unknown	Hwang et al., 2002	No
	PA-Rab5	<p>-</p>, <p>Mouse model of pathological Rab5 activation</p>		C57BL/6J	RAB5A		Mice carry a transgene encoding myc-tagged human Rab5a, under the control of a Thy-1 promoter.	RAB5A: Transgenic	Alzheimer's Disease	Enlarged Rab5-positive endosomes, tau hyperphosphorylation, synapse loss in hippocampus, and loss of basal forebrain cholinergic neurons.	When tested at 6 months of age, the performance of PA-Rab5 mice differed from wild-type controls in a novel object recognition test.		Available through Ralph Nixon.	Pensalfini et al., 2020	Yes
	PDAPP(line109)	<p>-</p>, <p>hAPP695Indiana</p>, <p>elan mouse</p>, <p>PDAPP</p>, <p>PD-APP</p>		C57B6 x DBA2	APP	APP V717F (Indiana)	A PDGF-driven human APP minigene with the V717F (Indiana) mutation. The construct contained APP introns 6-8 allowing alternative splicing of exons 7 and 8.	APP: Transgenic	Alzheimer's Disease	Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus.	Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months.	Alterations in sleep/wake states, thermoregulation, and motor activity.	Unknown	Games et al., 1995, Rockenstein et al., 1995	Yes
	PDGF-APPSw,Ind (line J9)	APP(Swedish,Indiana), line J9, hAPPJ9, hAPPlow		C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter.	APP: Transgenic	Alzheimer's Disease	Amyloid plaques at 8-10 months, but not at 2-4 months when deficits in synaptic transmission are observed. Approximately 20% of mice had plaques at 5-7 months, 50% at 8-10 months, and 100% by 21-25 months.	Unknown.	Deficits in synaptic transmission at 2-4 months, prior to amyloid deposition.	Available through Lennart Mucke	Hsia et al., 1999	No
	PDGF-APP(WT) (line I5)	<p>line I5</p>	B6.Cg-Tg(PDGFB-APP)5Lms/J	(C57BL/6 x DBA/2)F2	APP		APP-WT driven by the human PDGF-β promoter; an APP transgene with the Indiana mutation was converted to wild-type by PCR primer modification.	APP: Transgenic	Alzheimer's Disease	Expression of human APP in the brain especially in the neocortex and hippocampus. No plaques up to 24 months.	Unknown.		The Jackson Lab: Stock# 004662; Cryopreserved	Mucke et al., 2000	Yes
	PLB1-triple (hAPP/hTau/hPS1)	<p>hAPP/hTau/hPS1</p>, <p>PLB1(Triple)</p>		C57BL6	APP, MAPT, PSEN1	APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W	Targeted insertion of human APP and tau sequences at the HPRT site on the X chromosome, driven by mouse CaMKII-α. Human APP (isoform 770) with the Swedish and London mutations. Human tau (isoform 2N/4R, 441 amino acids) with P301L and R406W. APP/tau-expressing animals (PLB1-double) were crossed with hPS1 (A246E) transgenic mice (Borchelt et al., 1997) to generate the triple transgenic.	APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene	Alzheimer's Disease	Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT.	Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity.	Litter size and overall health were normal. Mice spent more time awake at six months and had fragmented sleep. Quantitative EEG showed heightened delta power during wakefulness and REM sleep.	Available through Bettina Platt	Platt et al., 2011	Yes
	PLB4 (hBACE1)	hBACE1		C57BL/6J, for at least six generations	BACE1		Targeted insertion of a single copy of human BACE1 at the HPRT locus on the X chromosome. Transgene expression driven by the mouse CaMKII-α promoter.	BACE1: Transgenic	Alzheimer's Disease	Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology.	Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety.	Breeding, litter size, and overall health are normal. Reduced body weight in knock-in animals after six months of age in males and nine months in females.	Available through Bettina Platt	Plucińska et al., 2014	Yes
	Plcγ2-P522R knock-in		Plcg2^em1Bwef	C57BL/6J	Plcg2		CRISPR/Cas9 was used to introduce the P522R mutation into the endogenous mouse Plcg2 gene. Knock-in mice were bred to homozygosity.	Plcg2: Knock-In	Alzheimer's Disease, Dementia with Lewy Bodies, Frontotemporal Dementia	Hypertrophic astrocytes in the hippocampi, revealed by GFAP immunohistochemistry. Microglial activation revealed by TSPO PET imaging.	Unknown.	A subset of DAM genes and genes related to Plcγ2 signaling, the neuronal cytoskeleton, and myelination are differentially expressed in the brains of knock-in mice, compared with wild-type animals.	Available through Christian Haass.	Takalo et al., 2020	Yes
	Plcg2 KO	<p>-</p>, <p>Plcg2 knock-out</p>	B6(SJL)-Plcg2^em2Adiuj/J	C57BL/6J	Plcg2		CRISPR/Cas9 was used to introduce a knock-out mutation into the mouse Plcg2 gene.	Plcg2: Knock-Out	Alzheimer's Disease	Unknown.	Unknown.		Available Fall, 2018 from The Jackson Laboratory, Stock# 29910	The Jackson Laboratory	Yes
	Plcg2M28L/APOE4/Trem2R47H		B6.Cg-Apoe^{tm1.1(APOE*4)Adiuj}Plcg2^em2AdiujTrem2^em1Adiuj/J	C57BL/6J	APOE, Plcg2, Trem2	TREM2 R47H	CRISPR/Cas9 was used to introduce the p.M28L mutation (methionine to leucine at position 28) into the Plcg2 gene of double mutant mice with a humanized APOE4 gene and the p.R47H point mutation knocked into the mouse Trem2 gene (B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj}Trem2^em1Adiuj/J, The Jackson Laboratory Stock# 028709).	APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 030674. Cryopreserved.	The Jackson Laboratory	Yes
	Plcg2*M28L x 5xFAD	<p>-</p>, <p>5xFAD<sup>M28L</sup></p>		C57BL/6J	Plcg2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Plcg2M28L/APOE4/Trem2R47H mice (JAX 030674) were backcrossed to C57BL/6J mice to remove the APOE4 sequence and Trem2 R47H mutation. The resulting Plcg2^M28L mice were then intercrossed with 5xFAD (JAX 034848) to create mice homozygous for the Plcg2 M28L mutation and hemizygous for the 5xFAD APP and PSEN1 transgenes.	Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Plaque burdens in the cortex and subiculum were elevated in 5xFAD^M28L mice but microglia showed less interaction with plaques, compared with 5xFAD.	Six-month-old 5xFAD^M28L and 5xFAD mice showed similar deficits in working memory, assessed in the Y-maze.	Impaired synaptic function—including deficits in basal synaptic transmission and long-term potentiation—similar to 5xFAD. Differences in microglial gene expression, compared with 5xFAD.	For Plcg2^M28Lmice, contact Andy Tsai. 5xFAD available from The Jackson Laboratory, JAX MMRRC Stock# 034848.	Tsai et al., 2023	Yes
	Plcg2*P522R	<p>-</p>, <p>Plcg2<sup>P522R</sup></p>, <p>Plcg2<sup>R522</sup></p>	B6.Cg-Plcg2^em1Msasn/J	C57BL/6J	Plcg2		CRISPR/Cas9 gene editing was used to introduce the P522R (c.1565 C>G ) mutation into the mouse Plcg2 gene in APOE4 Knock-In mice (JAX 027894). Correctly targeted mice were then backcrossed to C57BL/6J mice (JAX 000664) to remove the human APOE4 sequence.	Plcg2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.	Microglia in Plcg2P522R mice are more abundant, simpler in shape, and have lower levels of the PLCγ2 substrate, PIP2, than microglia in wild-type mice. Sight decrease in number of dendritic spines in hippocampal CA1 of Plcg2P522R mice, compared with wild-type mice.	Available from The Jackson Laboratory, Stock# 029598.	Maguire et al., 2021, Bevan et al.	Yes
	Plcg2*P522R x 5xFAD	<p>-</p>, <p>5xFAD<sup>P522R</sup></p>		C57BL/6J	Plcg2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	CRISPR/Cas9 gene editing was used to introduce the P522R mutation into the mouse Plcg2 gene in APOE4 Knock-In mice (JAX 027894). Correctly targeted mice were then backcrossed to C57BL/6J mice to remove the APOE4 sequence. The resulting Plcg2R522 mice (JAX 029598) were then intercrossed with 5xFAD (JAX 034848) to create mice homozygous for the Plcg2 P522R mutation and hemizygous for the 5xFAD APP and PSEN1 transgenes.	Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Plaque burdens in the cortex and subiculum were lower in 5xFAD^P522R mice and microglia showed increased interaction with plaques, compared with 5xFAD.	The PLCγ2 P522R variant protected against deficits in the Y-maze test of working memory in 5xFAD mice.	The PLCγ2 P522R variant protected against synaptic deficits in 5xFAD mice. Differences in microglial gene expression, compared with 5xFAD.	Plcg2^R522 available from The Jackson Laboratory, JAX Stock# 029598; 5xFAD available from The Jackson Laboratory, JAX MMRRC Stock# 034848.	Tsai et al., 2023	Yes
	Plcg2*P522R x APP NL-G-F	<p>-</p>, <p>Plcg2*P522R x APP<sup>NL-G-F</sup></p>, <p>Plcg2<sup>R522</sup> x APPNL-G-F</p>, <p>App<sup>NL-G-F</sup>R522</p>	B6.Cg-Plcg2^em1Msasn/J x App^tm3.1Tcs/App^tm3.1Tcs	C57BL/6	Plcg2, App	APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic)	Plcg2^R522 mice (JAX 029598) were intercrossed with APP^NL-G-F knock-in mice to create animals homozygous for the Plcg2 P522R mutation and the App modifications (a humanized Aβ region, and the Swedish, Iberian, and Arctic mutations linked to Alzheimer’s disease).	Plcg2: Knock-In; App: Knock-In	Alzheimer's Disease	Sex- and region-dependent increases in plaque burden, and decreases in microglia-plaque interactions, in Plcg2*P552R x APP^NL-G-F mice, compared with APP^NL-G-F.	Unknown.	The PLCγ2 P522R variant protected against synapse loss in APPNL-G-F mice.	Plcg2*P522R mice are available from The Jackson Laboratory, JAX Stock# 029598; APP^NL-G-F mice are available through Takaomi Saido.	Bevan et al.	Yes
	Prnp-APP	<p>-</p>, <p>APP(Prnp)</p>, <p>line A-2</p>	B6.Cg-Tg(Prnp-APP)A-2Dbo/J	C57BL/6	APP		Transgene expresses human APP driven by the mouse prion protein promoter.	APP: Transgenic	Alzheimer's Disease	Unknown.	Unknown.		Jackson Labs: Stock# 006006; Cryopreserved	The Jackson Laboratory	No
	PS19 with humanized TREM2 (common variant)	<p>-</p>, <p>PS19-TREM2<sup>CV</sup></p>, <p>PS19-T2<sup>CV</sup></p>		C57BL/6	MAPT, TREM2, Trem2	MAPT P301S	These mice carry a human MAPT transgene with the P301S mutation linked to frontotemporal dementia and a BAC transgene encoding the common variant of human TREM2, on a mouse-Trem2-null background.	MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia	Brain atrophy by 9 months of age. Increased microgliosis, astrogliosis and synapse loss, compared with PS19 mice carrying TREM2 with the R47H mutation.	Not known.	Increased expression of pro-inflammatory cytokines and DAM (disease-associated microglia) genes, compared with PS19 mice carrying TREM2 with the R47H mutation.	PS19 mice are available from The Jackson Laboratory (Stock# 008169). TREM2 mice are available through Marco Colonna.	Gratuze et al., 2020	Yes
	PS19 with humanized TREM2 (R47H)	<p>-</p>, <p>PS19-T2<sup>R47H</sup></p>, <p>PS19-TREM2<sup>R47H</sup></p>		C57BL/6	MAPT, TREM2, Trem2	MAPT P301S, TREM2 R47H	These mice carry a human MAPT transgene with the P301S mutation linked to frontotemporal dementia and a BAC transgene encoding the R47H variant of human TREM2, on a Trem2 knockout background.	MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia	Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2.	Not known.	Decreased expression of pro-inflammatory cytokines and DAM (disease-associated microglia) genes, compared with PS19 mice carrying the common variant of TREM2.	PS19 mice are available from The Jackson Laboratory (Stock# 008169). TREM2 mice are available through Marco Colonna.	Gratuze et al., 2020	Yes
	PS1(A246E)		Tg(Thy1-PSEN1*A246E)2Vln/0	FVB/N	PSEN1	PSEN1 A246E	Transgene human PSEN1 with the A246E mutation driven by the mouse Thy1 promoter.	PSEN1: Transgenic	Alzheimer's Disease	Histologically normal up to 2 years old by hematoxylin-eosin, silver, and thioflavin-S staining.	Learning and spatial memory were unaffected in the water maze test. Neither the escape latency nor escape pathway was different from PSEN1 wild-type mice at 1 and 9 months of age.	Mice are more sensitive to kainic acid displaying greater KA-induced seizure activity and neuronal damage. LTP induced by a strong stimulus was not altered, but a weak stimulation at synapses between Schaeffer’s collaterals and CA1 pyramidal neurons elicited LTP only in mutant mice.	No longer available through Paul van Dun	Schneider et al., 2001	No
	PS1 conditional Knock-out	PS1cKO, PSEN1 conditional KO	fPS1/fPS1;αCaMKII-Cre	CaM-Cre tg mice were generated in C57BL/6J x CBA hybrid, and then back-crossed several generations to C57BL/6J. The floxed PS1 mouse was generated in C57BL/6J and 129/Sv hybrid.	PSEN1		PS1 conditional KO mice with selective deletion of PSEN1 in excitatory neurons of the forebrain beginning about 1 month of age post-natally were generated by crossing a floxed PS1 mouse with a CamKII-Cre transgenic mouse.	PSEN1: Conditional Knock-out	Alzheimer's Disease	Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments.	Subtle but significant deficits in long-term spatial memory in the Morris water maze.		Available through Jie Shen	Yu et al., 2001	Yes
	PS1(M146L)	<p>-</p>, <p>PSEN1(M146L)</p>, <p>PS1 (M146L) line 5.1</p>		B6/D2/Swe/SJL mixed background	PSEN1	PSEN1 M146L (A>C)	Transgene containing human PSEN1 with the M146L mutation driven by the rat PDGF-β promoter.	PSEN1: Transgenic	Alzheimer's Disease	No abnormal pathology up to 2.5 years. Elevated Aβ2(43); no effect on Aβ40. Altered mitochondrial activity. Disregulation of calcium homeostasis.	No difference from wild-type mice in the “Y” maze (alternation performance or activity) at 12-14 weeks.	Elevated PSEN1 expression (2-3 fold). Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with wild-type mice. Larger calcium responses to depolarization. Stronger synaptic potentiation of the CA3 to CA1 projection.	Available through the Technology Transfer Office, Patents & Licensing, University of South Florida. The CRO PsychoGenics offers research services with this line.	Duff et al., 1996	No
	PS1(M146V)	PSEN1(M146V) (line 8.9)		Swiss Webster x B6D2F1	PSEN1	PSEN1 M146V	Transgene containing human PSEN1 with the M146V mutation driven by the rat PDGF-β promoter.	PSEN1: Transgenic	Alzheimer's Disease	No abnormal neuropathology up to 2.5 years. Elevated Aβ42(43). Altered mitochondrial activity and disregulation of calcium homeostasis.	Unknown.	Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with nontransgenic or mice transgenic for wild-type PSEN1.	Available through the Technology Transfer Office, Patents & Licensing, University of South Florida	Duff et al., 1996	No
	PS1 P264L	PS-1 P264L knock-in		R1 line of the ES cells (129 mouse strain)	PSEN1	PSEN1 P264L	An exon replacement strategy was used to generate mouse lines carrying a targeted mutation in their endogenous presenilin-1 gene. A proline-to-leucine substitution was targeted to codon 264 in exon 8 by homologous recombination in embryonic stem (ES) cells. Cre-lox system to remove the neomycin selection cassette from the targeted gene.	PSEN1: Knock-In	Alzheimer's Disease	Not observed.	Unknown.		Unknown	Siman et al., 2000	No
	PS2APP	<p>-</p>, <p>B6.PS2APP</p>, <p>TG B6.PS2APP mice (line B6.152H)</p>	Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz	C57BL/6	APP, PSEN2	APP K670_M671delinsNL (Swedish), PSEN2 N141I (Volga)	Coinjection of two transgenes into C57/Bl/6 zygotes: Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter and human APP751 with the Swedish mutation driven by the Thy1.2 promoter.	APP: Transgenic; PSEN2: Transgenic	Alzheimer's Disease	Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months.	Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months.	Decreased survival of newborn neurons in the dentate gyrus at about 4 months. Reduced endoplasmic reticulum Ca2+ and calcium dysregulation. A strong increase in LTP and post-tetanic potentiation (PTP) in hippocampal slices of 10 month old animals compared to wild-type mice. Decreased perfusion in the occipital cortex at all ages tested (10-17 months).	Available through Laurence Ozmen	Ozmen et al., 2009	Yes
	PS2APP (PS2(N141I) x APPswe)	<p>PS2(N141I) x APPswe</p>, <p>hPS2(N141I) x hAPPswe</p>	Tg(Thy1-APPSwe)71Jgr x Tg(Prnp-PSEN2*N141I)30Jgr	C57BL/6, DLB/2, crossed to C57BL/6	APP, PSEN2	APP K670_M671delinsNL (Swedish), PSEN2 N141I (Volga)	Double transgenics created by crossing APPSwe mice (transgene containing the 751 isoform of human APP with the Swedish mutation driven by the Thy1.2 promoter) with PS2(N141I) mice (tansgene containing human PSEN2 with the N141I mutation driven by the mouse prion protein promoter).	APP: Transgenic; PSEN2: Transgenic	Alzheimer's Disease	Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition.	Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze.	More insoluble Aβ40 and Aβ42 than age-matched APPSwe mice at 16-18 months. Loss of metabotropic glutamate receptors (mGlu2) in certain brain regions of aged mice as demonstrated by autoradiography.	Available through Laurence Ozmen	Richards et al., 2003	Yes
	PS2(N141I)	Prp-huPS2(N141I), PS2-N141I (line 30), hPS2mut	Tg(Prnp-PSEN2*N141I)30Jgr	Originally generated in a B6.D2 background, then crossed into C57BL/6J.	PSEN2	PSEN2 N141I (Volga)	Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter.	PSEN2: Transgenic	Alzheimer's Disease	Unknown.	Unknown.	Ubiquitous expression of mutant transgene. Brain homogenate from 2 week-old mice had PSEN levels 1.8-2.2 fold higher than wild-type mice. Disrupted Ca2+ homeostasis, similar to that of double transgenic PS2APP mice, including a reduction in endoplasmic reticulum Ca2+ content in cultured neurons and a generally decreased response to metabotropic agonists.	Available through Laurence Ozmen	Richards et al., 2003	No
	PS/APP	<p>-</p>, <p>PS1 + APP</p>, <p>PSAPP</p>, <p>APP/PS1</p>, <p>APP/PS1 double transgenic</p>		B6/D2/Swe/SJL mixed background	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C)	These double transgenic mice were generated by crossing mice overexpressing human APP with the Swedish mutation driven by the hamster prion protein gene promoter (the Tg2576 model) with mice overexpressing human PSEN1 with the M146L mutation driven by the PDGF-β promoter (PSEN1(M146L), line 5.1). The two transgenes segregate independently.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter, cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation.	Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels.	Selective increase in brain Aβ42(43) in the double transgenics (41% increase at 6 weeks) compared to Tg2576 single transgenic, which had unchanged Aβ40 and Aβ42(43) at this age.	Tg2576: Taconic (Stock #001349) and Charles River; PS1(M146L): University of South Florida Technology Transfer Office. The CRO PsychoGenics offers research services with Tg2576 and the double transgenic line.	Holcomb et al., 1998	Yes
	PS cDKO	PS1/PS2 cDKO, PSEN1/PSEN2 conditional double knock-out	fPS1/fPS1;αCaMKII-Cre;PS2-/-	C57BL6/129 hybrid	PSEN1, PSEN2		To generate forebrain-specific conditional double knockout mice lacking both PS1 and PS2 (PS cDKO) mice, floxed PS1 (fPS1), αCaMKII-Cre transgenic mice and PS2-/- mice were crossed together to obtain fPS1/fPS1;αCaMKII-Cre;PS2-/- mice.	PSEN1: Conditional Knock-out; PSEN2: Knock-Out	Alzheimer's Disease	At 2 months the number of apoptotic neurons is elevated about 8-fold. By 6 months, about 18 percent of of cortical neurons are lost. Up-regulation of inflammatory markers and progressive astrogliosis and microgliosis in the neocortex and hippocampus.	Impairments in hippocampal learning and memory as indicated by Morris water maze and contextual fear conditioning evident by 2 months and worsens with age.	Increased neurogenesis in the dentate gyrus.	Available through Jie Shen	Saura et al., 2004	Yes
	PSEN1-flox	<p>-</p>, <p>PS1 conditional KO</p>	B6;129P-Psen1^tm1Vln/J	Origin: 129P2/OlaHsd; backcrossed to C57BL/6	PSEN1		A targeting vector containing a neomycin resistance gene was inserted downstream of exon 7 of PSEN1; loxP sites were inserted on both sides of exon 7 and downstream of the neomycin resistance gene.	PSEN1: Knock-Out	Alzheimer's Disease	No morphological abnormalities. When crossed with Cre recombinase driven by Thy1, brain levels of Aβ40 and Aβ42 decrease and C-terminal fragments of APP accumulate.	When crossed with Cre recombinase driven by Thy1, no cognitive deficit in an object recognition task.	When crossed with Cre recombinase driven by Thy1, LTP induction is slightly altered.	The Jackson Lab: Stock# 007605; Cryopreserved	Dewachter et al., 2002	No
	PSEN1 Knock-out	<p>-</p>, <p>PS1<sup>-/-</sup></p>, <p>PS1-</p>, <p>PSEN1 null</p>, <p>Psen1<sup>tm1Shn</sup></p>, <p>PS1 null</p>	B6.129-Psen1^tm1Shn/J	C57BL/6	PSEN1		A targeting construct containing a neomycin cassette was used to disrupt exons 2 and 3 of the endogenous mouse PS1 gene.	PSEN1: Knock-Out	Alzheimer's Disease	Impaired neurogenesis. Massive neuronal loss. Hemorrhages in the CNS.	Unknown.	Homozygous mice die shortly after birth; heterozygous mutants are viable and fertile. Gross skeletal malformations.	The Jackson Lab: Stock# 003615; Cryopreserved	Shen et al., 1997	No
	PSEN1(M146V) Knock-In	<p>-</p>, <p>PS1M146V KI</p>, <p>PS1M146VKI</p>, <p>The Miles W. Miller Mouse</p>	B6.129-Psen1^tm1Mpm/J	C57BL/6	PSEN1	PSEN1 M146V	Point mutations were introduced into exon 5 of the endogenous mouse PSEN1 gene altering the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively. The targeting vector contained a lox-P flanked neomycin resistance cassette and herpes simplex virus thymidine kinase genes.	PSEN1: Knock-In	Alzheimer's Disease	Hypersensitive to kainate-induced degeneration and death of CA3, CA1 and hilar neurons. Cultured hippocampal neurons have increased vulnerability to death induced by glutamate. Disrupted calcium homeostasis. Increased oxidative stress and mitochondrial dysfunction.	Unknown.	Mice are viable, fertile, and normal in size. No gross physical or behavioral abnormalities.	The Jackson Lab: Stock# 004193; Cryopreserved	Guo et al., 1999	No
	PSEN1(P117L) (line 13)	line 13, PS1(P117L)		Mixed C57BL/6 and DBA/2J	PSEN1	PSEN1 P117L	Transgene of human PSEN1 with the P117L mutation driven by the neuron specific enolase (NSE) promoter.	PSEN1: Transgenic	Alzheimer's Disease	No plaques or diffuse amyloid deposits at 2-3 months. Elevated generation of Aβ42.	Unknown.	Express human PSEN1 at 2-3x the level of endogenous murine PSEN1. Impaired neurogenesis in the hippocampus.	No longer available	Wen et al., 2002	No
	PSEN1(WT)	PS1(WT), PSEN1 (wild-type)		Mixed C57BL/6J, DBA/2J	PSEN1		Human wild-type PSEN1 driven by neuron-specific enolase (NSE).	PSEN1: Transgenic	Alzheimer's Disease	No pathological changes have been observed in these mice.	Unknown.		No longer available	Wen et al., 2002	No
	PSEN1-YAC (line G9)	line G9, H163R mutant PS-1 YAC, B6-G9, PS1-YAC	B6.129S4-Tg(PSEN1H163R)G9Btla/J	Origin: 129S4/SvJae, backcrossed to C57BL/6	PSEN1	PSEN1 H163R	A 1000 kb YAC transgene (788H12) containing the entire human PSEN1 gene with the H163R mutation. Transgene also has ~550 kb of upstream and 350 kb of downstream flanking sequences.	PSEN1: Transgenic	Alzheimer's Disease	Elevated Aβ42 in the brain and plasma. Higher levels and earlier Aβ deposition when crossed with APP YAC line R1.40.	Unknown.	Alternatively spliced human PSEN1 transcripts.	The Jackson Lab: Stock# 006469; Cryopreserved	Lamb et al., 1999	No
	PSEN2 Knock-out	<p>-</p>, <p>PS2<sup>-/-</sup></p>, <p>PSEN2 null</p>, <p>PSEN KO</p>, <p>PS2 null</p>	B6.129P-Psen2^tm1Bdes/J	129P2/OlaHsd derived embryonic stem cells injected into C57BL/6 blastocysts; resulting chimeric mice backcrossed to C57BL/6J	PSEN2		A targeting vector containing a hygromycin resistance gene driven by the phosphoglycerate kinase promoter was used to disrupt exon 5 of PSEN2 by introducing a frame shift between exons 4 and 6.	PSEN2: Knock-Out	Alzheimer's Disease	No gross brain abnormalities or astrogliosis.	Unknown.	Alveolar wall thickening, pulmonary fibrosis, mild hemorrhage in the lungs.	The Jackson Lab: Stock# 005617; Cryopreserved	Herreman et al., 1999	No
	PWK.APP/PS1		PWK.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How	PWK/PhJ	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with PWK/PhJ mice for at least six generations.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques and plaque-associated gliosis by 8 months.	Transgenic mice are hyperactive and aggressive. Working memory and short-term memory are intact at 7 to 8 months, as assessed by tests in the Y-maze.		Available from The Jackson Laboratory, Stock #25971.	Onos et al., 2019	Yes
	rTg9191	<p>-</p>, <p>APP<sub>NLI</sub></p>		129S6FVB F1	APP	APP K670_M671delinsNL (Swedish), APP V717I (London)	These are bigenic mice with the CAMKII-α promoter driving expression of tetracycline transactivator (tTa) in excitatory neurons in the forebrain, and a responder transgene consisting of mutant human APP (isoform 695) carrying the Swedish and London mutations. The expression of the transgene is constitutive until suppressed by doxycycline.	APP: Transgenic	Alzheimer's Disease	Age-associated pathology in the cerebral cortex and hippocampus starting at 8 and 10½-12½ months of age, respectively. Gliosis and hyperphosphorylated tau in the vicinity of dense-core plaques. Fibrillar oligomeric species, e.g., Aβ dimers.	No transgene-related deficits seen in Morris water maze (4, 12, 21, 24, months of age) or fixed consecutive-number (23 months of age) tests.	Reduced body weight at 24-27 months relative to non-Tg littermates and those expressing only tTA.	Available through Karen Ashe	Liu et al., 2015	Yes
	rTgTauEC	<p>-</p>, <p>neuropsin-tTA x FVB-Tg(tetO-tauP301L)4510</p>		4510 mice are on an FVB background. Neuropsin-tTA mice are on a C57BL/6 background.	MAPT	MAPT P301L	Bigenic mice made by crossing an activator line, neuropsin-tTA, with a responder line, Tg(tetO-tauP301L)4510. The neuropsin promoter drives the tetracycline transactivator (tTA) transgene preferentially in a subset of entorhinal neurons. tTA drives expression of human tau (4R0N) with the P301L mutation. Transgene expression in bigenic mice is constitutive until suppressed by doxycycline.	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss.	Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test.	No apparent change in anxiety as assessed by the open field test. Reduced Arc induction in the hippocampus after contextual fear conditioning. Subtle differences in basal synaptic transmission with enhanced axonal excitability.	Unknown.	de Calignon et al., 2012	Yes
	rTg(tauP301L)4510	<p>-</p>, <p>rTg4510</p>, <p>rTg(tetO-TauP301L)4510</p>, <p>Tau P301L</p>	129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ; Fgf14^{Tg(tetO-MAPTP301L)4510Kha}/J. Formerly: 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ; FVB-Tg(tetO-MAPTP301L)#Kha/JlwsJ	Mixed: 129S6 (activator) X FVB (responder)	MAPT	MAPT P301L	Bi-transgenic mice are made by crossing an activator line, CaMKIIα-tTA, with a responder line, Tg(tetO-tauP301L)4510. The CaMKIIα promoter drives the tetracycline transactivator (tTA) transgene preferentially in forebrain neurons. tTA drives expression of human tau (4R0N) with the P301L mutation. Transgene expression in bi-transgenic mice is constitutive until suppressed by doxycycline.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60 percent) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (six to eight week) suppression of transgenic tau.	Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved.	Homozygous mice are not viable. It should be noted that disruption of an endogenous mouse gene, caused by random insertion of the MAPT transgene, significantly contributes to the neuropathological and neurodegenerative phenotypes observed in rTg4510 mice	4510 responder line: The Jackson Lab: Stock# 015815; Activator line: The Jackson Lab: Stock# 016198.	Santacruz et al., 2005, Ramsden et al., 2005, Gamache et al., 2019	Yes
	Senescence Accelerated Mouse (SAMP8)	<p>SAMP8</p>, <p>SAMP-8</p>, <p>SAM-P/8</p>, <p>SAM-P8</p>		AKR/J, suspected outbreeding to unknown line			One of several related strains developed from an AKR/J inbred line with a spontaneous accelerated aging phenotype.	Spontaneous	Alzheimer's Disease	Age-associated increase in hippocampal Aβ from 4 to 12 months, but no plaque-like structures by Congo red or thioflavine S. Spongiform degeneration: vacuoles of various size in the neuropil in the brain stem. Microglial cell proliferation. Degeneration of dopamine neurons in the substantia nigra and noradrenaline neurons in the locus coeruleus.	Age-associated behavioral impairments including learning and memory difficulties, emotional disorders (reduced anxiety-like behavior and depressive behavior) and altered circadian rhythms of spontaneous motor activity and drinking behaviours.		Envigo (formerly Harlan): SAMP8-TaHsd	Yagi et al., 1988	No
	Snx1D465N/APOE4/Trem2R47H		B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Snx1^em1Adiuj Trem2^em1Adiuj/J	C57BL/6J	Snx1, APOE, Trem2	TREM2 R47H	CRISPR/cas9 was used to generate a D465N mutation in the Snx1 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene.	Snx1: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 031942. Cryopreserved.	The Jackson Laboratory	Yes
	Sorl1*A528T		B6.Cg-Sorl1^em1Adiuj/J	C57BL/6J	Sorl1	SORL1 A528T (SNP 13)	CRISPR/Cas9 gene editing was used to introduce the A528T missense mutation and a silent mutation (R529R) into the mouse Sorl1 gene in APOE4/Trem2*R47H mice (JAX 028709). Correctly targeted mice were then backcrossed to C57BL/6J mice (JAX 000664) to remove the human APOE4 sequence and the Trem2 mutation.	Sorl1: Knock-In	Alzheimer's Disease				Available from The Jackson Laboratory, JAX Stock# 032759; cryorecovery.	The Jackson Laboratory	Yes
	Sorl1A528T/APOE4/Trem2R47H		B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Sorl1^em1Adiuj Trem2^em1Adiuj/J	C57BL/6J	Sorl1, APOE, Trem2	TREM2 R47H, SORL1 A528T (SNP 13), APOE C130R (ApoE4)	CRISPR/cas9 was used to generate a knock-in A528T mutation of the Sorl1 gene of APOE4/Trem2*R47H mice—double-mutant mice with a humanized Apoe (ε4 allele) gene and the R47H point mutation knocked into the mouse Trem2 gene.	Sorl1: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		The Jackson Laboratory, Stock# 031940. Cryopreserved.	The Jackson Laboratory	Yes
	SORL1 transgenic (Cre-inducible)	<p>-</p>, <p>Rosa26<sup>TgSORL1WT</sup></p>	Rosa26^TgSORL1WT	C57BL/6J	SORL1		SORL1 cDNA downstream of the cytomegalovirus early enhancer/chicken β-actin promoter and a floxed neomycin resistance cassette with a polyA stop element (neo-R) was introduced into the murine Rosa26 locus. Cre-mediated excision of neo-R induces SORL1 overexpression.	SORL1: Transgenic	Alzheimer's Disease	Unknown.	Normal performance in the Morris Water Maze.	Altered transciptome and phosphoproteome compared with wild-type mice. LTP and Morris Water Maze performance are insensitive to Aβ oligomers.	Available through Thomas Willnow.	Caglayan et al., 2014	Yes
	SORLA-deficient	<p>-</p>, <p>Sorl1 knockout</p>, <p>Sorl1<sup>-/-</sup></p>, <p>Lr11<sup>-/-</sup></p>, <p>Lr11<sup>ΔEx4</sup></p>		Generated on a mixed 129SvEmcTer X C57BL/6N genetic background, subsequently backcrossed to C57BL/6J.	Sorl1		The 5' region of exon 4 of the murine Sorl1 gene was replaced by a neomycin resistance cassette. The disrupted allele is expressed, and mice generate low levels of a dysfunctional SORLA protein lacking 54 amino acids within the N-terminal region of the VPS10P domain.	Sorl1: Knock-Out	Alzheimer's Disease	Mice do not generate amyloid plaques. Disrupted nigrostriatal connectivity and thinner inner nuclear layer of the retina.	Hyperactivity and reduced anxiety, compared with wild-type mice.	Deficits in salt homeostasis, lowered mean arterial blood pressure, decreased fat, and increased lean body mass. Increased neuronal ERK signaling and enhanced adult neurogenesis.	Available through Thomas Willnow.	Andersen et al., 2005, Dodson et al., 2008	Yes
	TAS10 (thy1-APPswe)	<p>thy1-APPswe</p>		Transgene injected into C57BL/6 x C3H oocytes, some backcrossing to C57BL/6	APP	APP K670_M671delinsNL (Swedish)	Transgene expresses human APP (isoform 695) harboring the Swedish mutation, driven by the murine Thy-1 promoter.	APP: Transgenic	Alzheimer's Disease	Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes.	Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning.	No differences in body temperature, locomotor activity, or Rotarod performance, relative to non-Tg controls.	Unknown	Richardson et al., 2003	Yes
	TASTPM (TAS10 x TPM)	<p>TAS10 x TPM</p>, <p>APPswe x PS1.M1466V</p>, <p>TAS/TPM</p>		TAS10 transgene originally injected into C57BL/6 x C3H oocytes, with some backcrossing to C57BL/6. TPM generated on pure C57BL/6 background.	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 M146V	This is a double transgenic model generated by crossing TAS10 mice (an APP transgenic line expressing human APP695 with the Swedish mutation) with TPM mice (a PSEN1 transgenic expressing human PSEN1 with the M146V mutation). Both transgenes are driven by the murine Thy-1 promoter.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Aβ deposits beginning at 3 months of age, with fibrillar plaques by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid. Plaques surrounded by dystrophic neurites and reactive glia. No tangles or neuronal loss. Female mice have more rapid and severe amyloid pathology.	Age-dependent impairment in object recognition memory starting around 6 months of age.		Unknown	Howlett et al., 2004	Yes
	Tau264	Tau(WT) transgenic (line 264)		B6C3F1 embryos, backcrossed to C57BL/6	MAPT		This transgenic mouse expresses 3-repeat (3R) and 4-repeat (4R) isoforms of wild-type human tau. The minigene, driven by the mouse CAMKIIα promoter, includes intronic sequences flanking exon 10, allowing for physiological splicing of exon 10.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	No overt neuropathology even at the advanced age of 24 months.	Comparable to non-Tg mice in Morris water maze tasks at 4 and 6 months of age.		Available through Hiroshi Mori and Takami Tomiyama	Umeda et al., 2013	No
	Tau35			C57BL/6 (75%) and 129/Ola (25%).	MAPT		A fragment of human tau (187-441 a.a.) expressed under control of the human tau promotor was inserted at the Hprt locus.	MAPT: Transgenic	Progressive Supranuclear Palsy, Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Progressive tau pathology in the hippocampus, including abnormally phosphorylated and misfolded tau, mislocalized tau, and tangle-like structures. Dystrophic neurites.	Impaired spatial learning and memory in the Morris water maze. Early motor impairments, including abnormal limb clasping, Rotarod deficits and decreased grip strength.	Muscle fibers in the quadriceps and latissimus muscles appeared to be degenerative/regenerative. Progressive spine curvature.	Unknown.	Bondulich et al., 2016	Yes
	Tau4RTg2652		B6.Cg-Tg(Thy-MAPT*)2652Gds	C57BL/6J	MAPT		This transgenic mouse overexpresses wild-type human tau (1N4R). The Thy1.2 promoter drives high levels of transgene expression in the CNS.	MAPT: Transgenic	Frontotemporal Dementia, Other Tauopathy, Alzheimer's Disease	Extensive pretangle pathology throughout the brain (e.g. phospho- tau) but no mature neurofibrillary tangles and only mild oligomeric tau, restricted to the CA1 region of the hippocampus. Dystrophic neurites and axonal pathology (spheroids). No overt neuronal loss.	Motor deficits develop with age, including decreased grip strength and impaired Rotarod performance. Cognitive deficits, indicative of impaired spatial learning and memory, as assessed by the Barnes maze.	Homozygous mice have reduced body weight, reduced fertility, and premature death. Some homozygous mice also exhibit seizure activity.	The MMRRC Stock# MMRRC:036717	Wheeler et al., 2015	Yes
	Tau609 (Tau 10 + 16)	Tau 10 + 16 , Tau(10+16 intron mutation)Tg, line 609		B6C3F1 embryos, backcrossed to C57BL/6	MAPT	MAPT IVS10+16 C>T	This model expresses a tau minigene driven by the mouse CAMKIIα promoter. The minigene encodes human tau 441, including partial intronic sequences flanking exon 10 of MAPT. The intronic mutation, IVS10 +16 C>T, was introduced by site-directed mutagenesis.	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease, Other Tauopathy	Aggregated tau in neurons of the entorhinal cortex, hippocampus, and cerebral cortex at advanced ages. Intraneuronal accumulation of tau oligomers in the hippocampus. Neuronal loss in the entorhinal cortex and hippocampus. Gliosis. Some hippocampal areas affected by age-related synaptic dysfunction and reduced synaptic density.	Impaired spatial reference memory as measured by the Morris water maze by 6 months of age.	Human tau transcripts containing exon 10 are over-represented in the adult mouse brain, leading to elevated levels of 4R tau relative to 3R tau.	Available through Hiroshi Mori and Takami Tomiyama	Umeda et al., 2013	Yes
	TauA152T-AAV	<p>-</p>, <p>Tau<sup>A152T</sup>-AAV</p>		C57BL/6	MAPT	MAPT A152T	An adeno-associated viral (AAV1) vector encoding TauA152T under the control of the cytomegalovirus enhancer/chicken β-actin promoter was injected bilaterally into the lateral ventricles of neonatal C57BL/6 mice.	MAPT: Virus	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Neuron loss and astrogliosis were observed in the cortices of 3-month-old mice.	Compared with GFP-AAV controls, Tau^A152T-AAV mice showed deficits in contextual and cued fear conditioning, increased hyperactivity, and decreased rearing in the open-field test, and spent more time in the open arms of the elevated plus maze. Tau^A152T-AAV mice also exhibited motor impairment on the Rotarod.		Unknown.	Carlomagno et al., 2019	Yes
	TauC3 (Transgenic caspase-cleaved tau)	<p>Transgenic caspase-cleaved tau</p>		BALB/C	MAPT		These transgenic mice express a truncated form of human tau (0N4R) that lacks the last 20 acids of the C-terminus, thus recapitulating the tau fragment produced by caspase cleavage (TauC3). Expression in the brain is driven by the promoter of the angiogenesis inhibitor 1 associated protein 4 (BAI1-AP4) gene.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	No significant cell loss or astrogliosis in the brain. Age-dependent reduction in synaptic proteins (e.g. synaptophysin, PSD95) by 1.3 to 3 months of age. Hyperphosphorylated tau oligomers and aggregates.	Learning and memory deficits by 1.3 to 3 months of age, as assessed by the Y-maze and passive avoidance tests. No significant motor impairment.	Normal lifespan.	Unknown	Kim et al., 2016	Yes
	Tau Exon 10 Knock-out	<p>-</p>, <p>mTau-E10-KO</p>		Mixed background (BALB/c x C57B1/B6 x B6D2F1)	MAPT		Gene-targeted deletion of exon 10 in murine tau gene.	MAPT: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia	No overt neuropathology at 12 months of age.	Age-dependent deterioration of sensorimotor functions, including coordination deficits on the Rotarod and a decrease in muscle strength. No deficits in learning or memory.	Humanized splicing pattern of murine tau, leading to the production of 3R tau rather than 4R tau. No anxiety phenotype.	Mice are no longer available, but frozen ES cells are available through Lars Nilsson or Astrid Gumucio	Gumucio et al., 2013	No
	TauΔK280 ("Proaggregation mutant")	<p>"Proaggregation mutant"</p>, <p>TauΔK</p>, <p>hTau40Δ280</p>		Unknown.	MAPT	MAPT K281del (K280del)	These are bigenic mice in which the TET-OFF system is used to temporally control human tau expression in the brain. Tetracycline transactivator (tTA) is downstream of the CAMKII-α promoter, driving expression in excitatory neurons in the forebrain. tTA in turn stimulates expression of the responder transgene, full-length human tau (hTau40, 2N4R) carrying the FTD-associated deletion, ΔK280.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Abundant pre-tangle pathology, but only rare mature tangles, and only at advanced ages. Tau pathology included mislocalization of tau to the somatodendritic compartment, aggregation, and hyperphosphorylation.	Unknown.		Available through Eva Mandelkow.	Eckermann et al., 2007	Yes
	Tau P301L	<p>-</p>, <p>Tau.P301L</p>, <p>hTau.P301L</p>, <p>Tau-4R-P301L</p>, <p>Tau(P301L)</p>	Thy1-hTau.P301L	FVB/N	MAPT	MAPT P301L	These transgenic mice overexpress the human Tau-4R/2N isoform bearing the P301L mutation under the control of the neuron-specific murine Thy1 promoter.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF.	Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months.	Premature death around 8-12 months, preceded by weight loss, hyperkyphosis, reduced activity, and upper airway dysfunction.	The CRO InnoSer offers research services with this line.	Terwel et al., 2005	Yes
	TauP301L-AAV	<p>-</p>, <p>Tau<sup>P301L</sup>-AAV</p>		C57BL/6	MAPT	MAPT P301L	An adeno-associated viral (AAV1) vector encoding TauP301L under the control of the cytomegalovirus enhancer/chicken β-actin promoter was injected bilaterally into the lateral ventricles of neonatal C57BL/6 mice.	MAPT: Virus	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Neurofibrillary tangles and gliosis, but no cortical neuron loss, at 6 months of age.	Hyperactivity in the open field, decreased time spent in the center of open field, more time spent in the open arms of the elevated plus maze, and deficits in cued and contextual fear conditioning at 6 months of age.		Unknown.	Cook et al., 2015	Yes
	Tau P301S (Line PS19)	<p>Line PS19</p>, <p>PS19Tg</p>	B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J	(C57BL/6 x C3H)F1	MAPT	MAPT P301S	Transgenic line expressing mutant human tau under the direction of the mouse prion protein (Prnp) promoter. The transgene codes for tau with four microtubule-binding domains and one N-terminal insert (4R/1N).	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis.	Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months.	Clasping and limb retraction when lifted by the tail at three months, followed by limb weakness and brain atrophy. Homozygous females do not mate.	The Jackson Lab: Stock# 008169; Live. The CROs Scantox Neuro and InnoSer offer research services with this model.	Yoshiyama et al., 2007	Yes
	TauPS2APP	<p>-</p>, <p>Triple transgenic</p>, <p>3Tg</p>	B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L)	C57BL/6, DBA/2; backcrossed to C57BL/6	APP, MAPT, PSEN2	APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I (Volga)	PS2APP mice (line B6.152H) x tau mice (line B6.TauP301L). PS2APP were generated by co-injecting two transgenic constructs: human PSEN2 (N141I mutation) and human APP (Swedish mutation) driven by the mouse prion promoter and the mouse Thy1 promoter respectively. The transgenic TauP301L mouse (line pR5) expresses the human tau40 isoform driven by the Thy1.2 promoter.	APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic	Alzheimer's Disease	Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss.	Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology.	Cortex-specific deficiencies in oxidative phosphorylation. Loss of mitochondrial membrane potential. Reduced cortical ATP. Increased superoxide anions and ROS compared to wild-type. No differences in APP expression, APP cleavage or Aβ accumulation compared to PS2APP. Levels of ptau422 increased in an age-dependent manner, but levels of ptau231 did not.	Available through Laurence Ozmen	Grueninger et al., 2010	Yes
	Tau R406W transgenic	<p>-</p>, <p>TgTauR406W</p>, <p>Tau R406W-CAMKII</p>		B6SJL/F1; backcrossed to C57BL/6J	MAPT	MAPT R406W	Human 4-repeat tau cDNA with the R406W mutation containing myc and FLAG tags at N-and C-terminal ends, respectively, and driven by the CaMK-II promoter.	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments.	Impairments in contextual and cued fear conditioning at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits.	No differences from wild-type in body weight, sensorimotor reflexes (acoustic startle response), or motor coordination (accelerating rotarod and pole tests). Attenuation of the Schaffer collateral-evoked neural response in hippocampal slices. Decrease in prepulse inhibition. Higher mortality.	Unknown	Tatebayashi et al., 2002	Yes
	TauRDΔK280 (“Proaggregation mutant”)	<p>“Proaggregation mutant”</p>, <p>TauRDΔ</p>, <p>TauRD</p>, <p>TauRD/ΔK280</p>, <p>TauRDΔK</p>		C57BL/6	MAPT	MAPT K281del (K280del)	Regulatable expression of an abbreviated human tau sequence (amino acids 244-372) encompassing the four microtubule-binding repeat domains and carrying the ΔK280 mutation. Transgene is driven by the forebrain-specific CAMKIIα promoter. TET-OFF system in which the transgene is regulated by the tetracycline transactivator (tTA) and turned off by administration of doxycycline.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Tau aggregates and tangles as early as 2-3 months after gene expression. Gallyas silver-positive neurons abundant in the entorhinal cortex and amygdala, spreading to the neocortex by 15 months. “Ballooned” neurons. Astrogliosis. Synaptic structural changes and reduced synaptic number. Hippocampal neuronal loss.	Reversible learning and memory deficits in the Morris water maze and passive avoidance test. No significant motor deficit, although slight reduction in Rotarod performance.	Missorting of tau into the somato-dendritic compartment. Calcium dysregulation at synaptic boutons. Deficits in synaptic plasticity, including LTP and LTD.	Unknown	Mocanu et al., 2008	Yes
	Tau V337M	MAPT V337M, Tg214		B6SJL/F1	MAPT	MAPT V337M	Human 4-repeat tau driven by the PDGF-β promoter. Tagged with myc and Flag on the N- and C-terminals respectively.	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure.	Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze.	The amount of mutant tau varied, but was generally less than one tenth of endogenous tau levels. In hippocampal slices there was attenuation of the Schaffer collateral-evoked neural response.	Unknown	Tanemura et al., 2002, Tanemura et al., 2001	Yes
	TBA42	<p>-</p>, <p>Truncated beta-amyloid 42</p>		C57BL6	APP		Transgenic vector expresses a human N-terminally truncated Aβ sequence (3-42) fused to thyrotropin-releasing hormone. The transgene is under the control of the murine Thy1.2 regulatory sequence. The glutamate at position 3 of Aβ was mutated to glutamine to facilitate pyroglutamate formation by the enzyme glutaminyl cyclase.	APP: Transgenic	Alzheimer's Disease	Intraneuronal accumulation of Aβ peptides in the hippocampus by 3 months and in cerebellar nuclei by 6 months. Marked gliosis in the hippocampus by 12 months. Very rare extracellular Aβ deposits.	Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at 3 or 6 months. Early and persistent decrease in anxiety in the elevated plus maze. Comparable to wild-type in general motor coordination at 3 and 6 months as indicated by the balance-beam test, but impairment at 12 months.		Available through Thomas Bayer	Wittnam et al., 2012	Yes
	TcMAC21	<p>-</p>, <p>Tc(HSA21q;MAC)1Yakaz</p>, <p>B6D2F1 TcMAC21</p>, <p>DS-MAC</p>, <p>HSA21-MAC Tc</p>	TcMAC21	B6/D2 (C57BL/6J (B6) x DBA/2J (D2))			TcMAC21 has a freely and stably-segregating hybrid mouse artificial chromosome (MAC) that contains a nearly complete long-arm of human chromosome 21 (Hsa21q; 34 MB including ~93 percent of protein-coding genes and ~79 percent of non-coding sequences).	Multi-transgene	Down's Syndrome, Alzheimer's Disease	Elevated APP, Aβ40, and Aβ42 in brain at 15–24 months, but no amyloid plaque pathology. Enlarged lateral ventricles and superior colliculus, and smaller cerebellum.	Learning and memory deficits.	Reduced body size and weight, retrusion of the midface skeleton and mandible, congenital heart defects of septation and outflow tract, hematological abnormalities. Also, hypermetabolism, raised body temperature, hyperactive, with altered glucose and insulin biology.	Available from Riken Animal Resource RBRC05796. Also available from The Jackson Laboratory #035561.	Kazuki et al., 2020	Yes
	TetO-APPSweInd (line 102)	<p>line 102</p>	B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax	C57BL/6 x C3HeJ; backcrossed to C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2.	APP: Transgenic	Alzheimer's Disease	APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest doxycycline sensitivity relative to lines 107 and 885.	Hyperactivity.		The Jackson Lab; available through the JAX MMRRC Stock# 034845; Cryopreserved	Jankowsky et al., 2005	No
	TetO-APPSweInd (line 107)	<p>line 107</p>	B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax	C57BL/6 x C3HeJ; backcrossed to C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2.	APP: Transgenic	Alzheimer's Disease	APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Intermediate expression of transgene and doxycycline sensitivity relative to lines 102 and 885.	Hyperactivity.		The Jackson Lab; available through the JAX MMRRC Stock# 034846; Cryopreserved	Jankowsky et al., 2005	No
	TetO-APPSweInd (line 885)	<p>line 885</p>	B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax	C57BL/6 x C3HeJ; backcrossed to C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2.	APP: Transgenic	Alzheimer's Disease	APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest transgene expression and highest doxycycline requirement relative to lines 102 and 107.	Hyperactivity.		The Jackson Lab; available through the JAX MMRRC Stock# 034834; Cryopreserved	Jankowsky et al., 2005	No
	Tg2576	<p>-</p>, <p>Hsiao mice</p>, <p>App-Swe</p>, <p>App-sw</p>, <p>APP(sw)</p>, <p>APPSwe</p>	B6;SJL-Tg(APPSWE)2576Kha	B6;SJL Mixed Background	APP	APP K670_M671delinsNL (Swedish)	The human APP gene (isoform 695) containing the double mutation K670N, M671L (Swedish mutation) under the control of the hamster prion protein.	APP: Transgenic	Alzheimer's Disease	Numerous parenchymal Aβ plaques by 11-13 months with some vascular amyloid. Oxidative lipid damage, astrogliosis and microgliosis. No tangles or neuronal loss.	Impaired spatial learning, working memory, and contextual fear conditioning reported at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months.	Between 7 -12 weeks males become aggressive and begin to fight. Premature mortality: mortality of >20% anticipated, particularly in males.	Taconic: Stock #1349. Charles River, PsychoGenics, and Scantox Neuro offer research services with this line.	Hsiao et al., 1996	Yes
	Tg2576/Tau(P301L) (APPSwe-Tau)	<p>APPSwe-Tau</p>, <p>APPSwe(2576)/TauJNPL3</p>, <p>TAPP</p>	Tg(APPSWE)2576Kha; Tg(Prnp-MAPT*P301L)JNPL3Hlmc	C57BL/6, DBA/2, SJL, SW Mixed Background	APP, MAPT	APP K670_M671delinsNL (Swedish), MAPT P301L	Generated by crossing Tg2576 mice, which have the transgene for human APP (isoform 695) carrying the Swedish mutation with mice expressing human MAPT (4 repeat) with the P301L mutation.	APP; MAPT: Transgenic	Alzheimer's Disease	Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis.	Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming.	Progressive hindlimb weakness. Hunched posture. Eye irritations. Some mice have the Pde6brd1 retinal degeneration mutation which can cause light sensitivity and/or blindness and may affect behavioral testing.	Taconic: Stock# 2469	Lewis et al., 2001	Yes
	Tg4-42	<p>-</p>, <p>Tg-Aβ(4-42)</p>		C57BL6	APP		Transgenic encodes N-truncated human Aβ (Aβ4-42) fused to the murine thyrotropin releasing hormone signal peptide under the control of the Thy1 promoter.	APP: Transgenic	Alzheimer's Disease	Aβ4-42 is dectable starting at two months, predominantly in the CA1 region of the hippocampus, but also in the occipital cortex, piriform cortex, striatum, and superior colliculus. Age- and dose-dependent hippocampal neuronal loss is seen in the CA1 region as well as microgliosis and astrogliosis.	Age-dependent spatial learning deficit as demonstrated in the Morris water maze, specifically, the absence of a preference for the target quadrant starting at eight months in homozygous mice and at 12 months in hemizygous mice. Impaired contextual fear conditioning.	Intact vision and motor abilities.	Available through Thomas Bayer.	Bouter et al., 2013	Yes
	TgAPParc		B6CBA-Tg(Thy1.2-hAPParc)	C57BL/6-CBA	APP	APP E693G (Arctic)	Transgenic mice with human APP (isoform 695) bearing the Arctic APP mutation (E693G).	APP: Transgenic	Alzheimer's Disease	Mild amyloid pathology with a relatively late onset, starting with intracellular Aβ, then diffuse extracellular Aβ deposits in the subiculum, expanding to interconnected brain regions such as retrosplenial granular cortex, thalamus, and mammillary bodies. Pathology more severe in females.	Spatial learning and memory deficit in the Barnes maze test in heterozygous females mice at 15 months.		Available through Annica Rönnbäck	Rönnbäck et al., 2011	No
	tg-APPSwe	<p>-</p>, <p>Tg-Swe</p>		C57BL/6J	APP	APP K670_M671delinsNL (Swedish)	Transgene with human APP (isoform 695) bearing the Swedish mutation under the murine Thy1 promoter.	APP: Transgenic	Alzheimer's Disease	Extracellular amyloid deposition begins at ~12 months. Intraneuronal Aβ aggregates at ~6 months. Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1.0% (at 12 months) and 2.8% (at 18 months).	Unknown.		Available through Lars Nilsson	Philipson et al., 2009, Lord et al., 2006	Yes
	TgAPPSwe-KI			R1 line of ES cells	APP	APP K670_M671delinsNL (Swedish)	Modification of mouse APP sequence to introduce the Swedish mutation and "humanize" the murine Aβ sequence by altering three amino acids.	APP: Knock-In	Alzheimer's Disease	Accumulation of human Aβ.	Unknown.		Unknown	Reaume et al., 1996	No
	Tg-ArcSwe	<p>-</p>, <p>tg ArcSwe</p>, <p>APP-ArcSwe</p>		C57BL/6J	APP	APP K670_M671delinsNL (Swedish), APP E693G (Arctic)	Transgene with human APP (isoform 695) containing both the Arctic (E693G) and Swedish (KM670/671NL) mutations under the murine Thy1 promoter.	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus.	Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months.	Tg-ArcSwe have reduced body weight compared with nontransgenic littermates.	Available through Stina Syvänen or Lars Nilsson.	Lord et al., 2006	Yes
	TgCRND8	<p>-</p>, <p>APP(swe/ind) CRND8</p>		Hybrid C3H/He-C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Transgene contains human APP695 with the Swedish mutation (KM670/671/NL) and Indiana mutation (V717F) under the control of the hamster prion (PrP) gene promoter. The expression cassette includes about 90 nucleotides of the APP 5'-untranslated region adjacent to the start codon and 269 nucleotides of the 3′-untranslated region.	APP: Transgenic	Alzheimer's Disease	Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months .	Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests.	Cholinergic dysfunction: decrease in the number of cholinergic neurons in the nucleus basalis magnocellularis by 7 months as measured by ChAT immunoreactivity. Enhanced auditory startle response and modest reduction in prepulse inhibition.	Available through the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto	Chishti et al., 2001	Yes
	TgDimer			C57BL/6N	APP	APP K670_M671delinsNL (Swedish), APP S679C	These transgenic mice express human APP (isoform 751) containing the Swedish (KM670/671NL) mutation and a serine-to-cysteine substitution at amino acid 679 (amino acid 8 within the Aβ sequence), under the control of the murine Thy1 promoter.	APP: Transgenic	Alzheimer's Disease, MCI due to AD	Intracellular Aβ immunoreactivity in the hippocampus and cortex, beginning by 12 months. No amyloid plaques, hyperphosphorylated tau, microgliosis, astrogliosis, or neuron loss through 24 months.	Learning deficits, as well as indicators of increased anxiety and depression, by 7 months.	More rapid decay of hippocampal long-term potentiation, compared with wild-type mice. Age-dependent cholinergic loss in hippocampus; lower rates of serotonin turnover in hippocampus, ventral striatum, and amygdala.	Available through Carsten Korth.	Müller-Schiffmann et al., 2016	Yes
	Tg-FDD	<p>-</p>, <p>BRI2(Tg-FDD)</p>		Hybrid C3HeB/FeJ embryo; crossed to C57BL/6J	ITM2B (BRI2)	BRI2: Familial Danish Dementia (FDD) duplication	The transgene, driven by the mouse prion promoter (Prnp), consists of the 795 form of human BRI(2) with a 10-nucleotide duplication-insertion (TTTAATTTGT).	ITM2B (BRI2): Transgenic	Familial Danish Dementia, Cerebral Amyloid Angiopathy, Alzheimer's Disease	Widespread cerebral amyloid angiopathy (CAA) starting around 7 months. Deposition of the Danish amyloid subunit (ADan) in brain parenchyma and vessels, along with amyloid-associated gliosis and inflammation, intracellular and extracellular deposition of oligomeric ADan, and tau-positive deposits in neuropil, but no neurofibrillary tangles.	Age-dependent abnormal grooming behavior. Around one year mice develop an arched back and walk with a wide-based gait and short steps. Feet clasping upon suspension of the mice by their tails.		Available through Ruben Vidal	Vidal et al., 2009	No
	Tg-mAPP/DN-RAGE	mAPP/DN-RAGE, APP/DN-RAGE		C57BL/6	APP, RAGE (AGER)	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Mice expressing a form of transgenic RAGE comprising a truncated form of the receptor with intact extracellular and membrane-spanning portions, but a deleted cytosolic tail driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661--now extinct).	APP: Transgenic; RAGE (AGER): Transgenic	Alzheimer's Disease	Diminished neuropathology compared with mice expressing mutant APP alone at both 3–4 and 14–18 months of age.	Preservation of spatial learning and memory compared with Tg-mAPP/RAGE animals.	No abnormalities with respect to reproductive fitness, development, basic neurological functioning, or longevity.	Available through Shirley ShiDu Yan	Arancio et al., 2004	No
	Tg-mAPP/RAGE	APP/RAGE		C57BL/6	APP, RAGE (AGER)	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Mice expressing human wild-type RAGE driven by the PDGF-β promoter were crossed with mice expressing human APP carrying the Swedish and Indiana mutations driven by PDGF-β promoter (The Jackson Lab: Stock# 004661-now extinct)	APP: Transgenic; RAGE (AGER): Transgenic	Alzheimer's Disease	Increased activation of microglia and astrocytes compared to mice expressing mutant APP alone.	Abnormalities in spatial learning and memory at 3-4 months of age, whereas deficits occur later in mice expressing mutant APP alone and are less severe.		Available through Shirley ShiDu Yan	Arancio et al., 2004	No
	Tg-SwDI (APP-Swedish,Dutch,Iowa)	<p>APP-Swedish,Dutch,Iowa</p>, <p>APPSwDI</p>	C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax	C57BL/6	APP	APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa)	Transgenic mice with 2.1 kb of the human APP gene (isoform 770) with the Swedish (K670N/M671L), Dutch (E693Q) and Iowa (D694N) mutations under the control of the mouse Thy1 promoter.	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type	Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months.	Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination.		The Jackson Lab; available through the JAX MMRRC Stock# 034843; Live	Davis et al., 2004	Yes
	THY-Tau22	<p>-</p>, <p>Tau22</p>		C57BL6/CBA; backcrossed to C57BL6	MAPT	MAPT G272V, MAPT P301S	Transgene containing the cDNA of the 412 amino acid isoform of human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2 promotor.	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis.	Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity.	Fertile with normal frequency and size of litters. Stably transmits the transgene to offspring. Deficits in hippocampal synaptic transmission.	Available through Luc Buée	Schindowski et al., 2006	Yes
	TMHT (Thy-1 mutated human tau)	<p>Thy-1 mutated human tau</p>, <p>TAU 441</p>, <p>hTAU441</p>, <p>TAU441 V337M R406W</p>		C57Bl/6xDBA	MAPT	MAPT V337M, MAPT R406W	Transgene consists of human MAPT Tau441 (2N/4R) with mutations V337M and R406W under control of the Thy1 promoter.	MAPT: Transgenic	Alzheimer's Disease	Increased total tau, and phosphorylated tau (Thr181, Ser199, Thr231) in amygdala and hippocampus starting at 3 months.	Spatial memory deficits starting at 5 months (Morris water maze). Olfactory deficits at 5 months (Buried food test). No motor deficits (rota rod, beam walk) or depressive behavior (forced swim test).	Olfactory deficits.	The CRO Scantox Neuro offers research services with this line.	Flunkert et al., 2013	Yes
	TPM (Thy-1 PS1.M146V)	<p>Thy-1 PS1.M146V</p>		Transgene injected into fertilized oocytes from pure C57BL/6 mice.	PSEN1	PSEN1 M146V	Transgene encoding human PSEN1 carrying the M146V mutation. Transgene is driven by the murine Thy-1 promoter.	PSEN1: Transgenic	Alzheimer's Disease	No plaques.	Unknown.		Unknown	Howlett et al., 2004	No
	TREM2-BAC	<p>-</p>, <p>BAC-TREM2</p>		FVB/NJ	TREM2		The BAC (RP11-237K15) transgene contains the TREM2 coding region and surrounding genomic regions (>50 kb on each side) with conserved gene regulatory elements. Key coding exons were deleted from other TREM-like genes contained in the BAC, to prevent their expression. Transgenic mice were generated and maintained on the FVB/NJ background.	TREM2: Transgenic	Alzheimer's Disease	No obvious neuropathology is observed at 4, 7 and 11 months of age.	Normal contextual fear conditioning at 10 months of age.	Normal LTP at 10 months of age.	Available through X. William Yang.	Lee et al., 2018	Yes
	TREM2-BAC X 5xFAD	<p>-</p>, <p>BAC-TREM2 X 5xFAD</p>		TREM2-BAC: FVB/NJ; 5xFAD: C57BL/6 X SJL	TREM2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	TREM2-BAC mice were crossed with 5xFAD mice.	TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques with plaque-associated microgliosis. Reduced plaque burden, altered microglial and plaque morphology, and less severe plaque-associated neuritic dystrophy, compared with 5xFAD.	5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired.		TREM2-BAC: Available through X. William Yang. 5xFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live	Lee et al., 2018	Yes
	Trem2 flox		B6(C3)-Trem2^{tm1c(EUCOMM)Wtsi}/AdiujJ	B6(C3)	Trem2		Targeted insertion of LoxP sites flanking exons 2 and 3 of the mouse Trem2 gene.	Trem2: Knock-In	Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease	No data.	No data.		The Jackson Lab: Stock# 029853; Live	The Jackson Laboratory	No
	Trem2-H157Y knock-in			C57Bl/6J	Trem2	TREM2 H157Y	CRISPR/Cas9 gene editing was used to introduce the H157Y mutation into the mouse Trem2 gene.	Trem2: Knock-In	Alzheimer's Disease	Microglial density and morphology did not differ between carriers of the H157Y variant and wild-type mice.	Trem2-H157Y knock-in did not differ from wild-type mice at 6 months of age in tests of anxiety, associative memory, and spatial working memory.	Enhanced hippocampal synaptic plasticity was observed in mice homozygous for the H157Y variant, compared with wild-type mice.	Available through Na Zhao (zhao.na@mayo.edu).	Qiao et al., 2023	Yes
	Trem2-H157Y x 5xFAD			C57Bl/6J	Trem2, APP, PSEN1	TREM2 H157Y, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	CRISPR/Cas9 gene editing was used to introduce the H157Y mutation into the mouse Trem2 gene. The resulting Trem2-H157Y knock-in mice were then intercrossed with 5xFAD mice.	Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Age-dependent effects on amyloid-β pathology and gliosis. At 4 months, plaque burdens, microgliosis, and astrogliosis were similar among genotypes. By 8.5 months, amyloid burdens, microgliosis, and astrogliosis were reduced in homozygous carriers of the H157Y variant, compared with 5xFAD mice homozygous for wild-type Trem2.	Unknown.	Increased TREM2 shedding, decreased TREM2 signaling, and accelerated Aβ42 clearance from the interstitial fluid in 5xFAD homozygous for Trem2 H157Y, compared with 5xFAD homozygous for wild-type Trem2. Downregulation of disease-associated microglia (DAM) genes, microglial immune-related genes, genes encoding inflammatory cytokines, and genes expressed by astrocytes in H157Y homozygotes.	Trem2-H157Y knock-in mice are available through Na Zhao (zhao.na@mayo.edu). 5xFAD mice are available from The Jackson Laboratory, JAX MMRRC Stock# 034848.	Qiao et al., 2023	Yes
	TREM2, humanized (common variant)	<p>-</p>, <p>CV<sup>+</sup>mTrem2<sup>−/−</sup></p>, <p>CV-KO</p>, <p>TREM2<sup>CV</sup></p>		C57BL/6 ×CBA, backcrossed for at least four generations to C57BL/6.	TREM2, Trem2		BAC transgenic mice carrying human TREM2 (common variant), TREML1, and TREML2 were backcrossed to Trem2 knockout mice to yield mice that express the common variant of human TREM2 in the absence of mouse Trem2.	TREM2: Transgenic; Trem2: Knock-Out	Alzheimer's Disease	Unknown.	Unknown.		TREM2 mice are available through Marco Colonna.	Song et al., 2018	Yes
	TREM2, humanized (common variant) X 5XFAD	<p>-</p>, <p>CV<sup>+</sup>mTrem2<sup>−/−</sup>5XFAD</p>		C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6	Trem2, TREM2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	BAC transgenic mice carrying human TREM2 (common variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the common variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5xFAD mice.	Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques surrounded by activated microglia.	No data.	Neurodegeneration-associated microglial activation markers elevated, compared with 5XFAD lacking TREM2.	TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live	Song et al., 2018	Yes
	TREM2, humanized (R47H)	<p>-</p>, <p>R47H<sup>+</sup>mTrem2<sup>−/−</sup></p>, <p>R47H-KO</p>, <p>TREM2<sup>R47H</sup></p>		C57BL/6 × CBA, backcrossed for at least four generations to C57BL/6.	TREM2, Trem2	TREM2 R47H	BAC transgenic mice carrying human TREM2 (R47H variant), TREML1, and TREML2 were backcrossed to Trem2 knockout mice to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2.	TREM2: Transgenic; Trem2: Knock-Out	Alzheimer's Disease	Unknown.	Unknown.		TREM2 mice are available through Marco Colonna.	Song et al., 2018	Yes
	TREM2, humanized (R47H) X 5XFAD	<p>-</p>, <p>R47H<sup>+</sup>mTrem2<sup>−/−</sup>5XFAD</p>		C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6	Trem2, TREM2, APP, PSEN1	TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	BAC-transgenic mice carrying the human TREM2 (R47H variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5XFAD mice.	Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant.	No data.		TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live	Song et al., 2018	Yes
	TREM2-IPD	<p>-</p>, <p>Trem2-IPD</p>	B6-Trem2em2Npa	C57BL/6J	Trem2		CRISPR/Cas9 gene editing was used to disrupt the ADAM10/17 recognition site on TREM2, changing histidine-157 to isoleucine (I), serine-158 to proline (P), and threonine-159 to aspartate (D).	Trem2: Knock-In	Alzheimer's Disease	At 3 months of age, TREM2-IPD mice had more Tmem119-positive microglia and a greater percentage of proliferating microglia than mice expressing wild-type Trem2.	Unknown.	Levels of soluble TREM2 were decreased and levels of cell-surface TREM2 were increased in TREM2-IPD mice, compared with wild-type. The IPD mutation accelerated microglial maturation and increased microglial phagocytic activity.	Available from Novartis Pharma AG under an MTA. Contact Ivan Galimberti (ivan.galimberti@novartis.com) or Derya Shimshek (derya.shimshek@novartis.com).	Dhandapani et al., 2022, Beckmann et al., 2023	Yes
	Trem2-IPDxAPP23xPS45	<p>-</p>, <p>TREM2-IPDxAPP23xPS45</p>, <p>APP23xPS45xIPD</p>		C57BL/6	Trem2, APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 G384A	Trem2-IPDxAPP23xPS45 mice have a modified murine Trem2 gene (resulting in disruption of the ADAM protease cleavage site after amino acid 157) and carry transgenes for human APP and PSEN1 with the AD-linked Swedish and G384A mutations, respectively.	Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, plaque-associated neuritic dystrophies, microgliosis. Pathology exacerbated in Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 mice expressing wild-type Trem2, at an early—but not late—stage of plaque deposition.	Unknown.	Microglial maturation accelerated in Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 mice expressing wild-type Trem2.	TREM2-IPD and PS45 mice are available from Novartis Pharma AG under an MTA. Contact Ivan Galimberti (ivan.galimberti@novartis.com) or Derya Shimshek (derya.shimshek@novartis.com). APP23 mice are available through The Jackson Laboratory Stock# 030504, Live.	Dhandapani et al., 2022	Yes
	Trem2 KO (Colonna)	<p>-</p>, <p>Trem2<sup>-/-</sup> (Colonna)</p>	C57BL/6 -TREM2^tm1cln	C57BL/6	Trem2		Inactivation of the mouse Trem2 gene by targeted deletion of exons 3 and 4	Trem2: Knock-Out	Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease	Microglial number remains constant and microglial size decreases with age in the corpus callosum of Trem2 KO mice, while microglial number increases and microglial size remains stable in wild-type mice.	No cognitive/behaviorial deficits observed.	Osteopenic. Impaired microglial response to experimental demyelination, middle cerebral artery occlusion, and facial nerve axotomy.	Available through Marco Colonna	Turnbull et al., 2006	Yes
	Trem2 KO (Colonna) x 5XFAD	<p>-</p>, <p>Trem2<sup>-/-</sup>5XFAD</p>, <p>mTrem2<sup>-/-</sup>5XFAD</p><p> </p>	C57BL/6 -TREM2^tm1cln; B6.Cg-Tg(APPSwFlLon,PSEN1M146LL286V)6799Vas/Mmja	C57BL/6	Trem2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	5XFAD mice were crossed with Trem2 KO mice. TREM2 KO: Targeted deletion of exons 3 and 4 of mouse Trem2. 5XFAD express two transgenes: 1) human APP with the Swedish, Florida and London mutations, containing the 5' untranslated region and driven by the mouse Thy1 promoter and 2) human PSEN1 with the M146L and L286V mutations driven by the mouse Thy1 promoter.	Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes.	No data.		Trem2 KO: available through Marco Colonna. 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live	Wang et al., 2015	Yes
	Trem2 KO (Colonna) x PS19	<p>-</p>, <p>Trem2<sup>-/-</sup>PS19</p>	C57BL/6 -TREM2^tm1cln; B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J	C57BL/6	Trem2, MAPT	MAPT P301S	Trem2 KO (Colonna) mice were crossed with PS19 mice. TREM2 KO: Inactivation of the mouse Trem2 gene was achieved by targeted deletion of exons 3 and 4. PS19: express human MAPT (1N4R) with the P301S mutation, driven by the mouse prion protein (Prnp) promoter.	Trem2: Knock-Out; MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	Microgliosis, astrogliosis, and brain atrophy in Trem2^-/-PS19 mice are greatly attenuated compared with Trem2^+/+PS19 animals.	No data.		Trem2 KO: available through Marco Colonna. PS19: The Jackson Lab: Stock# 008169; Live	Leyns et al., 2017	Yes
	Trem2 KO (JAX)		C57BL/6J-Trem2^em2Adiuj/J	C57BL/6J	Trem2		Trem2 expression was ablated using CRISPR/Cas9. Non-homologous end joining resulted in a 175-bp deletion that introduced a stop codon at amino acid 17.	Trem2: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease	No data..	No data.		The Jackson Lab: Stock# 027197; Live	The Jackson Laboratory	Yes
	Trem2 KO (KOMP)	<p>-</p>, <p>Trem2 −/− (KOMP)</p>	Trem2^{tm1(KOMP)Vlcg}	C57BL/6N	Trem2		The entire coding region of the Trem2 gene was replaced by Velocigene cassette ZEN-Ub1 (lacZ -p(A)-loxP-hUbCpro-neor-p(A)-loxP).	Trem2: Knock-Out	Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease	No data.	At six months, mice perform normally in the open-field test, elevated plus maze, three-chamber social-interaction test, and contextual and cued fear-conditioning test.	Trem2−/− microglia show a muted response to excitotoxicity in vivo, and decreased proliferation and increased apoptosis in vitro. Overexpression of Treml1 is driven by an ectopic Ubiquitin C promoter in the selection cassette.	UC Davis KOMP Repository, Project VG10093, cryo-recovery or sperm	Kang et al., 2018	Yes
	Trem2 KO (KOMP) x APPPS1	<p>-</p>, <p>APPPS1;Trem2<sup>-/-</sup></p>	TREM2^{tm1(KOMP)Vlcg}; B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr	C57BL/6	Trem2, APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 L166P	Trem2-/-: The entire coding region of the Trem2 gene was replaced by Velocigene cassette ZEN-Ub1 (lacZ-p(A)-loxP-hUbCpro-neor-p(A)-LoxP). APPPS1: Mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter.	Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Reduced plaque burden at early stages of plaque deposition but increased plaque burden at later stages, fewer plaque-associated myeloid cells and astrocytes, less phospho-tau in plaque-associated dystrophic neurites, compared with APPPS1.	No data.		APPPS1 available through Mathias Jucker; Trem2 KO available through UC Davis KOMP Repository, Project VG10093, cryo-recovery or sperm	Jay et al., 2015, Jay et al., 2017	Yes
	Trem2 KO (KOMP) x htau	<p>-</p>, <p>hTau;Trem2<sup>−/−</sup></p>	TREM2^{tm1(KOMP)Vlcg}; B6.Cg-Mapt^tm1(EGFP)Klt Tg(MAPT)8cPdav/J	C57BL/6	Mapt, MAPT, Trem2		Htau mice were bred to Trem2−/− mice (Trem2tm1(KOMP)Vlcg) to generate hTau;Trem2−/− and htau/Trem2+/+ mice. These mice were backcrossed for four generations, and maintained on a C57BL/6 background.	Mapt: Knock-Out; MAPT: Transgenic; Trem2: Knock-Out	Nasu-Hakola Disease, Alzheimer's Disease, Frontotemporal Dementia	Tau phosphorylation and aggregation in the cortex are enhanced in htau mice lacking TREM2, but reactive microglia are smaller and their processes have fewer branches.	No data.	Levels of stress-related protein kinases are elevated in the cortices and hippocampi of hTau;Trem2−/− compared with htau;Trem2+/+ mice.	htau: The Jackson Lab: Stock# 005491, live; research services with this line available from the CRO Scantox Neuro. Trem2 KO: UC Davis KOMP Repository, Project VG10093, cryorecovery or sperm.	Bemiller et al., 2017	Yes
	TREM2-mKATE2 Reporter Mouse	<p>-</p>, <p>TREM2 Reporter Mouse</p>	B6J-Trem2^{em4(mKate2)Bwef}	C57Bl/6J			CRISPR/Cas9 gene editing was used to insert the reporter construct into the mouse Trem2 locus, immediately downstream of exon 5. This construct contained a P2A (peptide 2A) sequence followed by mKate2 with the KDEL endoplasmic reticulum-retention sequence fused to its C terminus. Silent mutations were also introduced into Trem2 to aid in genotyping.		Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease	Unknown.	Unknown.	Bicistronic expression of endogenous Trem2 and the fluorescent protein mKate2 under control of the endogenous Trem2 promoter.	Available through Christian Haass.	Feiten et al.	No
	Trem2*R47H(HSS)	<p>-</p>, <p>Trem2*R47H<sup>HSS</sup></p>	B6.Cg-Trem2^em4Adiuj/J	C57BL/6J	Trem2	TREM2 R47H	CRISPR/Cas9 was used to edit the mouse Trem2 locus in the Trem2 R47H KI (JAX) model (JAX #27918), “humanizing” the cryptic splice acceptor site in exon 2 in the context of the existing R47H point mutation and two silent mutations.	Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		Register interest at The Jackson Laboratory, Stock No. 033781.	The Jackson Laboratory	Yes
	Trem2 R47H KI (Haass)	<p>-</p>, <p>R47H ki</p>	Trem2^{em2 Bwef}	C57BL/6N	Trem2	TREM2 R47H	CRISPR/Cas9 was used to introduce an R47H point mutation (arginine CGC > histidine CAC) and three silent mutations (glycine: GGG > GGT; arginine: AGA > CGA; lysine: AAG > AAA) into the mouse Trem2 gene. The silent mutations were added to aid in genotyping and increase the efficiency of gene editing.	Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.	R47H KI mice exhibit a gene-dose-dependent reduction in expression of Trem2, due to aberrant splicing of the mutant allele.	Available through Christian Haass.	Xiang et al., 2018	Yes
	Trem2 R47H KI (JAX)	<p>-</p>, <p>MODEL-AD R47H</p>, <p>Trem2R47H<sup>CSS</sup> (for cryptic splice site)</p>, <p>B6.Trem2R47H</p>	C57BL/6J-Trem2^em1Adiuj/J	C57BL/6J	Trem2	TREM2 R47H	CRISPR/Cas9 was used to introduce an R47H missense mutation and two silent mutations—to aid in genotyping and increase gene-editing efficiency—into the mouse Trem2 gene.	Trem2: Knock-In	Alzheimer's Disease	No neuron loss, amyloid plaques, or neurofibrillary tangles were observed in mice up to 24 months of age.	Locomotor activity, motor coordination, and working memory similar to wild-type at 2 and 12 months of age.	Compared with wild-type mice: age-, sex-, and region-dependent differences in glucose uptake and cerebral blood flow; increased mortality of females at 24 months of age; downregulation of genes related to immune function, and degradation of biological material in aged mice.	The Jackson Lab:Stock# 027918; Cryorecovery.	Kotredes et al., 2021, Tran et al., 2023	Yes
	Trem2 R47H KI (Lamb/Landreth)	<p>-</p>, <p>Trem2<sup>+/R47H</sup></p>		C57BL6/J	Trem2	TREM2 R47H	CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene.	Trem2: Knock-In	Alzheimer's Disease	No 6E10- or Thioflavin S-positive amyloid plaques were observed at 4 months of age.	Unknown.	Approximate 40 percent decrease in levels of Trem2 mRNA in cortices of Trem2+/R47H mice compared with Trem2+/+ mice.	Available through Gary Landreth or Bruce Lamb.	Cheng-Hathaway et al., 2018	Yes
	Trem2 R47H KI (Lamb/Landreth) X APPPS1-21	<p>-</p>, <p>APPPS1-21;Trem2<sup>+/R47H</sup></p>		C57BL6/J	Trem2, APP, PSEN1	TREM2 R47H, APP K670_M671delinsNL (Swedish), PSEN1 L166P	To create Trem2^+/R47Hmice,CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene. APPPS1-21 mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter.	Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, fewer plaque-associated myeloid cells, and worse plaque-associated neuritic dystrophy, compared with APPPS1-21 mice homozygous for wild-type Trem2.	Unknown.	Levels of Trem2 transcripts were reduced in APPPS1-21;Trem2+/R47H compared with APPPS1-21;Trem2+/+ and were similar to those in APPPS1-21 mice haploinsufficient for Trem2.	Trem2^+/R47H available through Gary Landreth or Bruce Lamb; APPPS1-21 available through Mathias Jucker.	Cheng-Hathaway et al., 2018	Yes
	Trem2 R47H KI x APOE4 (LOAD1)	<p>LOAD1</p>, <p>APOE4/Trem2R47H</p>, <p>APOE4/Trem2R47H</p>, <p>APOE4.Trem2R47H</p>	B6(SJL)-Apoe^{tm1.1(APOE*4)Adiuj} Trem2^em1Adiuj/J	C57BL/6J	APOE, Trem2	TREM2 R47H, APOE C130R (ApoE4)	This double-mutant line was generated by crossing APOE4 KI mice (Jackson Lab Stock# 027894), which carry a humanized APOE4 gene, to Trem2 R47H KI mice (Jackson Lab Stock # 027918), which have an R47H missense mutation knocked into the mouse Trem2 gene.	APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	No neuron loss, amyloid plaques, neurofibrillary tangles, vascular leakage, myelin loss, or reactive microglia in mice up to 24 months of age.	Age-related changes in locomotor activity, motor coordination, and working memory, but no genotype-dependent differences through 24 months of age, compared with wild-type mice.	Age-, sex-, and region-dependent differences in glucose uptake and cerebral blood flow, compared with wild-type mice. Increased mortality at 24 months of age. Down-regulation of genes related to immune function and degradation of biological material in aged mice.	The Jackson Lab:Stock# 028709; Live	Kotredes et al., 2021	Yes
	Trem2*R47H(NSS)	<p>-</p>, <p>Trem2*R47H<sup>NSS</sup></p>	B6(SJL)-Trem2^em1Aduci/J	C57BL/6J	Trem2	TREM2 R47H	CRISPR/Cas9 was used to edit the mouse Trem2 gene, introducing the R47H point mutation and 10 silent mutations in exon 2.	Trem2: Knock-In	Alzheimer's Disease	Changes in microglial morphology at 4 months but not 12 months, compared with wild-type.	Unknown.	Age-dependent synaptic deficits and age-dependent differences in gene expression, compared with wild-type mice. When crossed with 5xFAD mice, blunted inflammatory responses at 4 months, but exaggerated responses at 12 months.	Available from The Jackson Laboratory, Stock No. 034036.	Tran et al., 2023, The Jackson Laboratory	Yes
	Ts65Dn	<p>-</p>, <p>Segmentally trisomic Ts(17<sup>16</sup>)65Dn</p>, <p>Down syndrome-segmental trisomy 16</p>	B6EiC3Sn a/A-Ts(17¹⁶)65Dn/J	B6/C3H			Cesium irradiation produced a reciprocal translocation of chromosomes 16 and 17, creating a freely segregating, supernumerary chromosome Mmu1716 (17¹⁶).	Multi-transgene	Down's Syndrome, Alzheimer's Disease	Elevation of APP and soluble Aβ in the brain without Aβ plaque pathology. Changes to tau 3R/4R splicing, augmenting tau mRNA stability and tau phosphorylation. Basal forebrain neurodegeneration; loss of NE neurons in locus coeruleus; hippocampal abnormalities; cholinergic neuron loss; reduced number of proliferating cells. Neuroinflammation and oxidative stress markers.	Spatial learning and memory deficits, developmental delay in sensorimotor milestones, locomotor hyperactivity, lack of behavioral inhibition, and stereotypic behavior. Delayed motor acquisition, impaired coordination, reduced attention.	Reduced birthweight, muscular trembling, male sterility, blindness, and an abnormal facial appearance. Altered skeletal, pulmonary, immune, and cardiac functions. Vocalization and swallowing abnormalities. Elevated blood levels of Aβ40 and Aβ42.	Available from The Jackson Lab: Stock# 001924. Also available as a strain without blindness from The Jackson Lab Stock# 005252.	Davisson et al., 1990, Reeves et al., 1995	Yes
	WSB.APP/PS1		WSB.Cg-Tg(APPswe,PSEN1dE9)85Dbo/How	WSB/EiJ	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	Mice carry two transgenes, a chimeric mouse/human APP with the Swedish mutation and human PSEN1 lacking exon 9, each controlled by the mouse prion protein promoter. Transgenic mice on a congenic C57BL/6J background were backcrossed with WSB/EiJ mice for at least six generations.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in cortex and hippocampal area CA1 in females.	Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in females (data from males is not available, as wild-type males are unable to perform this test).		Available from The Jackson Laboratory, Stock #25970.	Onos et al., 2019	Yes
Rat Models (19)
	AAV-AD	<p>-</p>, <p>AgenT</p>		Wistar	APP, PSEN1	APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M146L (A>C)	Adeno-associated viral vectors separately encoding human APP with the Swedish and London mutations and human PSEN1 with the M146L mutation were injected bilaterally into the hippocampi of young adult (8-week-old) rats.	APP: Virus; PSEN1: Virus	Alzheimer's Disease	Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection. Anti-phospho-tau immunostaining suggests the presence of (pre)tangle-like structures. No astrogliosis seen up to 30 months post-injection.	Compared with control rats at 8 months post-injection, AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training and less time in the center of the open field.	At 8 months post-injection, long-term potentiation was impaired in hippocampal slices obtained from AAV-AD rats, compared with controls, but the groups did not differ with regards to long-term depression.	Viral vectors are available through AgenT SAS under collaboration or partnership agreements.	Audrain et al., 2017	Yes
	APP21		F344-Tg(APP)21Besey	Fischer 344	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	A lentiviral vector carrying a human APP₆₉₅ transgene was injected into Fischer 344 zygotes. This transgene contains the Swedish and Indiana mutations and is driven by the ubiquitin-C promoter.	APP: Transgenic	Alzheimer's Disease	No plaques to 30 months of age. Necrotic neurons in hippocampus and cortex by 19 months, in females; neuron loss not observed in cortices of 19-month males.	Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.		Available from the Rat Resource & Research Center, Stock# 00636; cryorecovery, sperm	Agca et al., 2008	Yes
	App knock-in (humanized Aβ)	<p>-</p>, <p>App<sup>h</sup></p>, <p>App<sup>h/h</sup></p>		Long-Evans	App		Three point mutations were introduced into the rat App gene to humanize the Aβ sequence (G5R, F10Y, and R13H of Aβ).	App: Knock-In	Alzheimer's Disease	No plaques, neurofibrillary tangles, or neuron loss observed at three months, the oldest age reported.	Unknown.		Available through Luciano D'Adamio.	Tambini et al., 2019	Yes
	App knock-in (humanized Aβ) (Leuven)	<p>-</p>, <p>App<sup>hu/hu</sup></p>		Long Evans	App		CRISPR/Cas9 was used to introduce the following mutations into the endogenous App gene: G676R (G5R), F681Y (F10Y), R684H (R13H), numbered according to the 770 amino-acid isoform of human APP (position within the Aβ sequence).	App: Knock-In	Alzheimer's Disease	No plaques or tangles were observed up to two years of age.	Unknown.	Levels of CTFβ and Aβ are elevated in the brains of these knock-in rats, compared with wild-type animals.	Available through Lutgarde Serneels.	Serneels et al., 2020	Yes
	App knock-in (humanized Aβ) (Leuven); Psen1 knock-in (M139T)	<p>-</p>, <p>App<sup>hu/hu</sup>;Psen1M139T<sup>+/+</sup></p>		Long Evans	App, Psen1	PSEN1 M139T	Crispr/Cas9 was used to humanize the Aβ sequence within the rat App gene and to introduce the M139T mutation into the rat Psen1 gene.	App: Knock-In; Psen1: Knock-In	Alzheimer's Disease	No plaques or tangles were observed up to 2 years of age.	Unknown.	Elevated levels of CTFβ and Aβ compared with wild-type rats. Increased Aβ42/Aβ40 ratio relative to rats homozygous for humanized App, but without the Psen1 mutation.	Available through Lutgarde Serneels.	Serneels et al., 2020	Yes
	App knock‐in (Icelandic mutation and humanized Aβ)	<p>-</p>, <p>App<sup>p</sup></p>		Long-Evans	App	APP A673T (Icelandic)	Four point mutations were introduced into the rat App gene to humanize the Aβ sequence (G5R, F10Y, and R13H of Aβ) and to add the Icelandic mutation A673T (numbered as in the 770-amino-acid isoform of human APP).	App: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		Available through Luciano D'Adamio.	Tambini et al., 2020	Yes
	App knock‐in (Swedish mutation and humanized Aβ)	<p>-</p>, <p>App<sup>s</sup></p>		Long-Evans	App	APP K670_M671delinsNL (Swedish)	Five point mutations were introduced into the rat App gene to humanize the Aβ sequence (G5R, F10Y, and R13H of Aβ) and to add the AD-linked Swedish double mutation, KM670/671NL (numbered as in the 770-amino-acid isoform of human APP).	App: Knock-In	Alzheimer's Disease	No plaques, neurofibrillary tangles, or neuron loss observed at 3 months, the oldest age reported.	Unknown.	Increased amplitude and decreased frequency of miniature excitatory postsynaptic currents; deficits in paired-pulse facilitation at excitatory synapses.	Available through Luciano D'Adamio.	Tambini et al., 2019, Tambini et al., 2020	Yes
	App NL-G-F Knock-in Rat	<p>-</p>, <p>App<sup>NL-G-F</sup> rat</p>, <p>APP Swe-Arc-Ibe knock-in rat</p>		Sprague Dawley	App	APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP I716F (Iberian)	This rat line, created using CRISPR/Cas9 technology, carries a humanized Aβ sequence (G676R, F681Y, and R684H) and three AD-linked mutations (Swedish, KM670/671NL; Arctic, E693G; and Iberian, I716F) in the endogenous rat App gene.	App: Knock-In	Alzheimer's Disease	Amyloid plaques apparent as early as 1 month in homozygous knock-ins. No neurofibrillary tangles through 22 months of age, but increases in tau phosphorylation, aggregation, and conformational changes. Astrogliosis, microgliosis, synapse and neuron loss.	Deficits in the Morris Water Maze task and a paired associate learning task as early as 5 and 7 months of age, respectively.		Available through Bai Lu.	Pang et al., 2022	Yes
	APP+PS1			Fischer 344	APP, PSEN1	APP K670_M671delinsNL (Swedish), APP V717F (Indiana), PSEN1 L166P	APP+PS1 transgenic rats express human APP with the Swedish and Indiana mutations and human PSEN1 with the L166P mutation. Both transgenes are driven by the ubiquitin-C promoter.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age.	Deficits in Barnes maze by 10 months of age.		Unknown.	Agca et al., 2016, Klakotskaia et al., 2018	Yes
	Mapt knockout rat (Cy23)	<p>Cy23</p>		Sprague-Dawley	Mapt		These tau knockout rats were created through transcription activator-like effector nuclease (TALEN)-mediated targeting of exon 2 of the rat Mapt gene.	Mapt: Knock-Out	Alzheimer's Disease	None reported.	Unknown.	No gross phenotypes reported.	Contact David Westaway, Institute for Neurodegenerative Diseases, UCSF.	Ayers et al., 2024	No
	McGill-R-Thy1-APP			HsdBrl:WH Wistar	APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	Transgene contains entire coding region of human APP₇₅₁ with the Swedish and Indiana mutations and approximately 900 bp of 3' non-translated sequence, driven by the murine Thy1.2 promoter.	APP: Transgenic	Alzheimer's Disease	Hemizygotes: intraneuronal Aβ in hippocampus and cortex by one week, but no plaques even at advanced ages. Homozygotes: intraneuronal Aβ in hippocampus and cortex by one week; amyloid plaques in hippocampus beginning at 6 months, in cortex beginning at 13 months.	Cognitive deficits are apparent by three months of age in both hemizygous and homozygous transgenic rats.	Resting-state fMRI showed disrupted cingulate network connectivity by 9 to11 months; FDG-PET showed hypometabolism by 16 to 19 months (homozygotes).	Breeding pairs available via a royalty agreement with McGill University; contact Adriana Ducatenzeiler.	Leon et al., 2010	Yes
	Psen1 L435F knock-in	<p>-</p>, <p>Psen1<sup>LF</sup></p>		Long-Evans	Psen1, App	PSEN1 L435F	Rats carry a mutation in the endogenous Psen1 gene that is homologous to the human L435F mutation, as well as a humanized Aβ sequence within the endogenous App gene.	Psen1: Knock-In; App: Knock-In	Alzheimer's Disease	None observed in 15-day-old rats.	Unknown.	Levels of Aβ43 are elevated in the brains of homozygous and heterozygous Psen1 mutation carriers.	Available through Luciano D’Adamio.	Tambini and D'Adamio, 2020	Yes
	SHR24			SHR	MAPT		SHR24 rats express a gene encoding amino acids 151-274 and 306-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R).	MAPT: Transgenic	Alzheimer's Disease	Neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem, beginning at 9 to 10 months. No neuron loss was observed in the hippocampus or cortex.	SHR24 rats exhibit age-dependent impairments in several neurobehavioral tests; hind-limb clasping during the tail-hang test is one of the earliest abnormalities to appear, evident by 3.5 months of age.	SHR24 rats have a shorter lifespan (approximately 14 months) than wild-type SHR rats (22-24 months).	Unknown.	Filipcik et al., 2012, Valachova et al., 2018	Yes
	SHR318			SHR	MAPT		SHR318 rats express a gene encoding amino acids 151-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R).	MAPT: Transgenic	Alzheimer's Disease	Neurofibrillary tangles first appear at 9 months and are particularly prominent in the brainstem and spinal cord. Axonal degeneration is observed in the brainstem and spinal cord of 10- to 12-month animals.	At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze. Reflexes and sensorimotor coordination are impaired at 7 months.	SHR72 rats have a shorter lifespan (approximately 10–12 months) than wild-type SHR rats (22–24 months).	No longer available.	Zilka et al., 2006, Hrnkova et al., 2007	Yes
	SHR72			SHR	MAPT		SHR72 rats express a gene encoding amino acids 151-391 of human tau, driven by the mouse Thy1 promoter (the numbering of amino acids corresponds to that of the 441-amino acid isoform of human tau, variously referred to as tau 40, Tau-F, or 2N4R).	MAPT: Transgenic	Alzheimer's Disease	Neurofibrillary tangles, demonstrated by Gallyas silver stain, were found the brainstems and spinal cords of terminal stage (7- to 8-month old) animals. Chromatolytic neurons and damaged axons were also observed at this stage.	Sensorimotor deficits and loss of muscle strength are apparent at 3 months. This stage lasted about three months, and then rats experienced a rapid, dramatic decline in neurological function, succumbing within several days.	SHR72 rats have a shorter lifespan (approximately 7-8 months) than wild-type SHR rats (22-24 months).	Unknown.	Koson et al., 2008	Yes
	SHRSP/FAD			Spontaneously hypertensive stroke-prone (SHRSP); Fischer 344	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	TgF344-AD rats, which carry human APP and PSEN1 transgenes, with the AD-linked Swedish and Δ exon 9 mutations, respectively, were backcrossed with spontaneously-hypertensive-stroke-prone (SHRSP) rats.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease, Vascular Dementia	Amyloid plaques, microgliosis, and possible astrogliosis. Occasional neurons appear to contain paired helical filament tau. Demyelination. Reduced calbindin immunoreactivity and increased levels of caspase-cleaved actin may indicate neuron loss.	Hyperactive. Working memory deficits as assessed by novel object recognition, but not as assessed by spontaneous alternation in the Y-maze.	Hypertensive.	Available through Sally Frautschy.	Denver et al., 2019	Yes
	Tg12099 rat			Sprague-Dawley	MAPT	MAPT P301S	Tg12099 rats express the 0N4R isoform of human MAPT with P301S mutation linked to frontotemporal dementia, driven by the rat Prnp promoter.	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	Tau pathology, including neurofibrillary tangles, forebrain neurodegeneration, and astrogliosis in homozygotes. Hemizygotes exhibit little pathology, save for a few AT8-immunoreactive neurons in the entorhinal cortices of aged animals.	Ataxia, bradykinesia, and seizures reported in aging homozygotes.	Premature death of homozygotes, with median survival of 14 months.	Contact David Westaway, Institute for Neurodegenerative Diseases, UCSF.	Ayers et al., 2024	Yes
	TgF344-AD			Fischer 344	APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	TgF344-AD rats express human APP with the Swedish mutation and human PSEN1 with the Δ exon 9 mutation. Both transgenes are driven by the mouse prion promoter.	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, microgliosis, and astrogliosis by 6 months. Neurofibrillary tangle-like structures at 16 months. Approximate 40 percent loss of neurons in hippocampus and cortex by 16 months.	Earliest reported deficits are in reversal learning in the Morris water maze, apparent by 6 months.		TgF344-AD rats on a Fischer344/NHsd background are available from the Rat Resource & Research Center, Stock# 00699.	Cohen et al., 2013	Yes
	Trem2 R47H knock-in	<p>-</p>, <p>Trem2<sup>R47H</sup></p>		Long-Evans	Trem2, App	TREM2 R47H	Rats carry the R47H mutation in the endogenous Trem2 gene and a humanized Aβ sequence within the endogenous App gene.	Trem2: Knock-In; App: Knock-In	Alzheimer's Disease	Unknown.	Unknown.		Available through Luciano D'Adamio.	Tambini and D'Adamio, 2020	Yes

When visualized, these phenotypes will distributed over a 18 month timeline demarcated at the following intervals: 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.

3xTg

Observed

X
Plaques at 26

Extracellular Aβ deposits by 6 months in the frontal cortex, predominantly layers 4 and 5 and progress with age (Oddo et al., 2003).
X
Tangles at 52

By 12 months extensive tau immunoreactivity in CA1 neurons of the hippocampus, particularly pyramidal neurons, later in the cortex. No tau pathology at 6 months (Oddo et al., 2003).
X
Gliosis at 30

Increased density of GFAP immunoreactive astrocytes and IBA-1 immunoreactive microglia compared with wild-type mice at 7 months (Caruso et al., 2013). Development of gliosis may occur earlier.
X
Changes in LTP/LTD at 26

By 6 months decreased LTP compared with wild type controls. Impairment in basal synaptic transmission. No change at 1 month of age (Oddo et al., 2003).
X
Cognitive Impairment at 17

Cognitive impairment manifests at 4 months as a deficit in long-term retention and correlates with the accumulation of intraneuronal Aβ in the hippocampus and amygdala, but plaques and tangles are not yet apparent (Billings et al., 2005).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Psen1, APP, MAPT	APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V	Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic	Alzheimer's Disease	Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles.	Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task.

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5xFAD (B6SJL)

Observed

X
Plaques at 8

Extracellular amyloid deposition begins around 2 months, first in the subiculum and layer V of the cortex. Aβ42 also accumulates intraneuronally in an aggregated form within the soma and neurites starting at 1.5 months.
X
Neuronal Loss at 23

Neuron loss in cortical layer V and subiculum.
X
Gliosis at 9

Gliosis begins at 2 months.
X
Synaptic Loss at 16

Levels of the presynaptic marker synaptophysin begin to decline by 4 months; levels of syntaxin, another presynaptic marker, and PSD-95, a postsynaptic marker, decline by 9 months
X
Changes in LTP/LTD at 25

Basal synaptic transmission and LTP in hippocampal area CA1 begin to deteriorate between 4 and 6 months
X
Cognitive Impairment at 18

Impaired spatial working memory in the Y-maze test and impaired remote memory stabilization in a contextual-fear-conditioning test by 4 to 5 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles.	Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype.

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5xFAD (C57BL6)

Observed

X
Plaques at 8

Amyloid plaques observed in hippocampus, cortex, thalamus, and spinal cord. Amyloidosis more severe in females than males.
X
Neuronal Loss at 52

Approximate 40 percent loss of layer V pyramidal neurons at one year.
X
Gliosis at 8

Microgliosis and astrogliosis are associated with amyloid plaques; microgliosis is associated with vascular damage.
X
Synaptic Loss at 24

Spine density was reduced in pyramidal neurons in somatosensory and prefrontal cortices, but not in the hippocampi, of 5xFAD mice crossed with mice expressing yellow fluorescent protein (YFP mice), compared with mice expressing YFP alone.
X
Changes in LTP/LTD at 8

LTD was induced in layer V cortical neurons of 8- to 10-week-old 5xFAD mice using the same protocol that induced spike-timing-dependent LTP in neurons of non-transgenic mice. LTP at Schaffer collateral-CA1 synapses was decreased in 5xFAD by 4 months of age.
X
Cognitive Impairment at 24

Impairments of spatial working memory and reduced anxiety emerge between 3 and 6 months and worsen with age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer V.	Age-dependent memory deficits, motor phenotype, and reduced anxiety.

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A7 APP transgenic

Observed

X
Plaques at 39

These mice develop progressive amyloid deposition in the cerebral cortex by 9-12 months. By 21 months of age amyloid pathology is extensive.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP T714I (Austrian)	APP: Transgenic	Alzheimer's Disease	Progressive amyloid deposition in the cerebral cortex by approximately 9-12 months.	Unknown.

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AAV-AD

Observed

X
Plaques at 128

Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection.
X
Changes in LTP/LTD at 40

Deficits in LTP as Schaffer collateral-CA1 synapse at 10 months (8 months post-injection). LTD similar to controls.
X
Cognitive Impairment at 40

AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M146L (A>C)	APP: Virus; PSEN1: Virus	Alzheimer's Disease	Amyloid plaques and cerebral amyloid angiopathy observed 30 months post-injection. Anti-phospho-tau immunostaining suggests the presence of (pre)tangle-like structures. No astrogliosis seen up to 30 months post-injection.	Compared with control rats at 8 months post-injection, AAV-AD spent less time in the target quadrant of the Morris water maze in probe tests administered 3 and 5 days after training and less time in the center of the open field.

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AAV-sTREM2 5xFAD

Observed

X
Plaques at 28

When examined at 7 months of age, amyloid plaque burdens in the hippocampus and cortex of AAV-sTREM2 5xFAD mice were about half those of 5xFAD mice injected with control vector.
X
Gliosis at 28

The number of plaque-associated microglia was increased in AAV-sTREM2 5xFAD mice examined at 7 months of age.
X
Changes in LTP/LTD at 24

Long-term potentiation at Shaeffer collateral-CA1 synapses is impaired in 5xFAD mice. AAV-mediated over expression of sTREM2 rescued LTP in AAV-sTREM2 5xFAD mice.
X
Cognitive Impairment at 24

5xFAD mice show impaired learning and memory in the Morris water maze, but AAV-sTREM2 5xFAD mice performed as well as non-transgenic controls.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
TREM2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	TREM2: Virus; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	AAV-mediated over expression of sTREM2 decreased amyloid plaque burdens and increased numbers of plaque-associated microglia in the brains of 5xFAD mice.	5xFAD mice show impaired learning and memory in the Morris water maze, but AAV-sTREM2 5xFAD mice performed as well as non-transgenic controls.

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AAV-sTREM2 PS19

Observed

X
Synaptic Loss at 28

AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.
X
Changes in LTP/LTD at 29

LTP at Shaeffer collateral-CA1 synapses was slightly enhanced in hippocampal slices from 7-month-old AAV-sTREM2 PS19 mice, compared with PS19 mice who had received control vector.
X
Cognitive Impairment at 30

AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
TREM2, MAPT	MAPT P301S	TREM2: Virus; MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.	AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze.

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Abca7A1527G/APOE4/Trem2R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Abca7, APOE, Trem2	TREM2 R47H	Abca7: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Abca7 KO/APOE4/Trem2*R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Abca7, APOE, Trem2	TREM2 R47H	Abca7: Knock-Out; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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ADanPP

Observed

X
Plaques at 9

Vascular amyloid deposits and punctate parenchymal aggregates first occur in the hippocampus and increase with age, spreading throughout the brain, including the cortex, amygdala, thalamus, and brainstem in hemizygous mice.
X
Gliosis at 17

Astrogliosis and microgliosis increase with age and increasing ADan-amyloid deposition.
X
Cognitive Impairment at 78

The only ages tested were 6 months and 18-20 months. Mice 18-20 months of age exhibited both motor and spatial learning defects in the Morris water maze, and increased anxiety in the open field test. No impairments were observed in 6 month-old mice.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
ITM2B (BRI2)	BRI2: Familial Danish Dementia (FDD) duplication	ITM2B (BRI2): Transgenic	Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy	ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present.	Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype.

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AD-BXD

Observed

X
Plaques at 24

Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, the earliest age examined. The extent of plaque deposition is strain-dependent.
X
Gliosis at 25

Strain-dependent gliosis by 6 months.
X
Cognitive Impairment at 60

In the AD-BXD population as a whole, transgenic mice performed similarly to non-transgenic littermates in a contextual fear-conditioning test at 6 months, but were impaired at 14 months. The age of onset and severity of impairment are strain-dependent.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Transgenic AD-BXD mice develop amyloid plaques by 6 months of age, although the extent of plaque deposition is strain-dependent.	Transgenic AD-BXD mice exhibit cognitive deficits, assessed using contextual fear conditioning. The age of onset and severity of impairment are strain-dependent.

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APOE2 Knock-In, floxed (CureAlz)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE		APOE: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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APOE3 Knock-In, floxed (CureAlz)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE		APOE: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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APOE3 Knock-In (Lamb)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE		APOE: Knock-In	Alzheimer's Disease, Traumatic Brain Injury	Unknown.	Unknown.

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APOE4 Knock-In, floxed (CureAlz)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE		APOE: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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APP21

Observed

X
Neuronal Loss at 76

Necrotic neurons in hippocampus and cortex of female rats.
X
Gliosis at 64

Activated (MHCII-positive) microglia present in white matter tracts at 15 months.
X
Cognitive Impairment at 12

Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	APP: Transgenic	Alzheimer's Disease	No plaques to 30 months of age. Necrotic neurons in hippocampus and cortex by 19 months, in females; neuron loss not observed in cortices of 19-month males.	Male rats show deficits in Morris water maze as early as 3 months of age. Females show deficits in Barnes maze at 14 months of age.

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APP23

Observed

X
Plaques at 26

Congophillic, dense-core amyloid plaques first appear at 6 months, and increase in size and number with age. Amyloid plaques can occupy more than 25% of the neocortex and hippocampus in 24 month-old mice (Sturchler-Pierrat et al., 1997; Calhoun et al., 1998).
X
Neuronal Loss at 61

Neuronal loss (14-28%) has been reported in the CA1 region of the hippocampus in 14-18 month old mice (Calhoun et al., 1998).
X
Gliosis at 26

Activated microglia in close proximity to dense amyloid plaques (Stalder et al., 1999). Upregulation of neuroinflammatory markers and activation of astrocytes and macrophages. Age-associated increase in components of the complement system, namely C1q and C3, at later ages (9 and 18 months, respectively) (Reichwald et al., 2009).
X
Cognitive Impairment at 13

Spatial memory defects in Morris Water maze at 3 months and progresses with age (Van dam et al., 2003; Kelly et al., 2003).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish)	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages.	Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages.

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APP23 x PS1-R278I

Observed

X
Plaques at 26

By 6 months of age amyloid plaques accumulate in the cortex and hippocampus. A high percentage of plaques are thioflavin-S –positive cored plaques.
X
Gliosis at 39

Astrocytosis in the vicinity of plaques in the hippocampus and cortex by 9 months.
X
Cognitive Impairment at 13

Short-term memory deficits are apparent by 3 to 4 months as measured by the Y maze.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	PSEN1 R278I	APP: Transgenic; PSEN1: Knock-In	Alzheimer's Disease	Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques.	Short-term memory deficits apparent by 3-4 months as measured by the Y maze.

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APP751SL/PS1 KI

Observed

X
Plaques at 11

Aβ deposition at 2.5 months compared to 6 months in APPSL mice. At 6 months, numerous compact Aβ deposits in the cortex, hippocampus, and thalamus, whereas in age-matched APPSL mice only very few deposits restricted mainly to the subiculum and deeper cortical layers. At 10 months, deposits increased in distribution, density, and size in both models (Casas et al., 2004).
X
Neuronal Loss at 23

Some cell loss detectable as early as 6 months in female mice. At 10 months extensive neuronal loss (>50%) is present in the CA1/2 hippocampal pyramidal cell layer. SNeuronal loss also occurs in the frontal cortex and cholinergic system (Casas et al., 2004; Christensen et al., 2008; Christensen et al., 2010).
X
Gliosis at 11

Astrogliosis occurs in parallel with Aβ deposition, starting around 2.5 months, and in proximity to Aβ-positive neurons (Wirths et al., 2010).
X
Synaptic Loss at 24

At 6 months, levels of pre- and post-synaptic markers are reduced (Breyhan et al., 2009).
X
Changes in LTP/LTD at 28

At 6 months there is a large reduction of long-term potentiation and disrupted paired pulse facilitation. No deficit at 4 months (Breyhan et al., 2009).
X
Cognitive Impairment at 27

Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates (Wirths et al., 2008).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), APP V717I (London), PSEN1 M233T, PSEN1 L235P	APP: Transgenic; PSEN1: Knock-In	Alzheimer's Disease	Acceleration of extracellular Aβ deposition compared to the single transgenics. Age-dependent neuronal loss in the hippocampus with extensive neuronal loss in the CA1/2 at 10 months with detection as early as 6 months in female mice. Intraneuronal Aβ and thioflavin-S-positive deposits before neuronal loss. Astrogliosis in proximity of Aβ-positive neurons.	Age-dependent impairments in working memory as measured by the Y maze and T-maze continuous alternation task. No deficit at 2 months, but deficits at 6 and 12 months compared to PS1KI littermates.

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APPDutch

Observed

X
Gliosis at 126

Microgliosis develops after the onset of CAA pathology and is prominent in areas adjacent to amyloid-laden vessels. There is also widespread activation of astrocytes in neocortical regions affected by CAA. These changes have been reported at 29 months of age, although the actual onset of gliosis may occur earlier than has been examined.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP E693Q (Dutch)	APP: Transgenic	Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease	Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed.	Unknown.

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APP E693Δ-Tg (Osaka)

Observed

X
Neuronal Loss at 104

Neuronal loss, as measured by NeuN staining, was observed in the CA3 region of the hippocampus at 24 months of age. Neuronal loss was not detected in the cerebral cortex at this time.
X
Gliosis at 52

At 12 months of age, microgliosis is seen in transgenic mice, as measured by the presence of Iba-1 staining in the hippocampus and cortex. Astrocytosis, as measured by GFAP-reactivity, increased starting around 18 months of age in these regions.
X
Synaptic Loss at 34

Starting around eight months of age, transgenic mice exhibit a decrease in synaptic density in the CA3 region of the hippocampus as measured by synaptophysin staining.
X
Changes in LTP/LTD at 35

By eight months of age, transgenic mice exhibit reduced short term plasticity as measured by paired-pulse facilitation in addition to reduced LTP as elicited by high frequency stimulation to the perforant pathway.
X
Cognitive Impairment at 36

By 8 months of age, transgenic mice exhibit memory impairment in the Morris water maze compared to mice expressing equivalent levels of wild-type human APP.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP E693del (Osaka)	APP: Transgenic	Alzheimer's Disease	Age-dependent accumulation of Aβ oligomers within hippocampal and cortical neurons, but negligible deposits of extracellular amyloid. Abnormal tau phosphorylation, but no overt tangle pathology. Synaptic loss and gliosis in hippocampus and cerebral cortex. Late neuronal loss in the CA3 region of the hippocampus.	Memory impairment by eight months as measured by the Morris water maze. Specifically, reduced spatial reference memory in the Morris water maze compared to mice expressing comparable levels of wild-type human APP.

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App knock-in (humanized Aβ)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App		App: Knock-In	Alzheimer's Disease	No plaques, neurofibrillary tangles, or neuron loss observed at three months, the oldest age reported.	Unknown.

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App knock-in (humanized Aβ)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App		App: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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App knock-in (humanized Aβ) (Leuven)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App		App: Knock-In	Alzheimer's Disease	No plaques or tangles were observed up to two years of age.	Unknown.

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App knock-in (humanized Aβ) (Leuven); Psen1 knock-in (M139T)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App, Psen1	PSEN1 M139T	App: Knock-In; Psen1: Knock-In	Alzheimer's Disease	No plaques or tangles were observed up to 2 years of age.	Unknown.

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App knock‐in (Icelandic mutation and humanized Aβ)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App	APP A673T (Icelandic)	App: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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App knock‐in (Swedish mutation and humanized Aβ)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App	APP K670_M671delinsNL (Swedish)	App: Knock-In	Alzheimer's Disease	No plaques, neurofibrillary tangles, or neuron loss observed at 3 months, the oldest age reported.	Unknown.

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App KO/APOE4/Trem2*R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, App, Trem2	TREM2 R47H	APOE: Knock-In; App: Knock-Out; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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APP NL-F Knock-in

Observed

X
Plaques at 26

Homozygotes develop amyloid plaques starting at 6 months in the cortex and hippocampus. Heterozygotes develop amyloidosis after 24 months. Plaques contained Aβ_1-42 and pyroglutamate Aβ (Aβ_3(pE)-42); Aβ_x-40was a minor species.
X
Gliosis at 26

Microglia and activated astrocytes accumulate with age, starting around 6 months of age, concurrent with plaque formation.
X
Synaptic Loss at 39

Reduced synaptophysin and PSD95 immunoreactivities associated with Aβ plaques at 9-12 months.
X
Cognitive Impairment at 78

Memory impairment in homozygous mice at 18 months as measured by the Y maze test. APP^NL/NL mice (with Swedish mutation only) were unimpaired at this age. No significant deficit was seen in the Morris water maze at 18 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP I716F (Iberian)	APP: Knock-In	Alzheimer's Disease	Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.	Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze.

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APP NL-G-F Knock-in

Observed

X
Plaques at 9

Aggressive amyloidosis; plaques develop in homozygous mice starting at 2 months with near saturation by 7 months. Aβ deposition at 4 months in heterozygous mice. Cortical and subcortical amyloidosis present.
X
Gliosis at 9

Microglia and activated astrocytes accumulate with age starting around 2 months, especially around plaques in a manner concurrent with plaque formation.
X
Synaptic Loss at 17

Reduction of synaptophysin and PSD95 immunoreactivities associated with Aβ plaques in both cortical and hippocampal areas.
X
Cognitive Impairment at 26

Memory impairment in homozygous mice by 6 months of age as measured by the Y maze.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic)	APP: Knock-In	Alzheimer's Disease	Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APP^NL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.	Memory impairment by 6 months as measured by the Y maze.

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App NL-G-F Knock-in Rat

Observed

X
Plaques at 4

Amyloid plaques apparent as early as 1 month in homozygous knock-ins, 4 months in heterozygotes. Amyloid pathology progresses more rapidly in females than males.
X
Neuronal Loss at 52

Reduced brain weight, fewer neurons in the hippocampus and cortex, and enlarged lateral ventricles seen at 12 months.
X
Gliosis at 24

Astrogliosis and microgliosis, particularly pronounced around amyloid plaques, were observed in homozygous knock-in rats at 6 months of age. Gliosis was also seen in year-old heterozygotes.
X
Synaptic Loss at 24

Decreased levels of the presynaptic marker synaptophysin and the postsynaptic marker PSD-95 in knock-in rats. Quantitative electron microscopy showed reductions in synaptic density, area, and perimeters in the hippocampus, entorhinal cortex and prefrontal cortex of knock-in brains.
X
Cognitive Impairment at 20

Deficits in the Morris Water Maze task and a paired associate learning task as early as 5 and 7 months of age, respectively.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App	APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP I716F (Iberian)	App: Knock-In	Alzheimer's Disease	Amyloid plaques apparent as early as 1 month in homozygous knock-ins. No neurofibrillary tangles through 22 months of age, but increases in tau phosphorylation, aggregation, and conformational changes. Astrogliosis, microgliosis, synapse and neuron loss.	Deficits in the Morris Water Maze task and a paired associate learning task as early as 5 and 7 months of age, respectively.

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AppNL-G-F/MAPT double knock-in

Observed

X
Plaques at 8

Plaques observed at 2 months.
X
Gliosis at 16

Astrogliosis and microgliosis observed by 4 months.
X
Cognitive Impairment at 52

Deficits in the Y-maze test of working memory at 12 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App, MAPT	APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic)	App: Knock-In; MAPT: Knock-In	Alzheimer's Disease	Amyloid plaques, plaque-associated neuritic dystrophy, and neuroinflammation, similar to App^NL-G-F.	Deficits in the Y-maze test of working memory, similar to App^NL-G-F.

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APPPS1

Observed

X
Plaques at 6

Aβ deposition begins at 6 weeks of age in the cortex and 3-4 months of age in the hippocampus (Radde et al., 2006).
X
Neuronal Loss at 74

Global neuron loss is not observed, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuronal density in 17-month old animals (Rupp et al., 2011).
X
Gliosis at 6

Activated microglia around Aβ deposits at 6 weeks as well as increased astrogliosis (Radde et al., 2006). Levels of CCL2 and TNFα increase at later ages (Lee et al., 2010).
X
Synaptic Loss at 10

Dendritic spine loss around plaques reported to begin approximately 4 weeks after plaque formation and continue for several months (Bittner et al., 2012).
X
Changes in LTP/LTD at 35

Hippocampal CA1 LTP normal at 4.5 months of age, but impaired at 8 and 15 months of age (Gengler et al., 2010).
X
Cognitive Impairment at 30

Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 L166P	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.	Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months.

Genes

Mutations

Modification

Disease

Neuropathology

Behavior/Cognition

APP, PSEN1

APP K670_M671delinsNL (Swedish), PSEN1 L166P

APP: Transgenic; PSEN1: Transgenic

Alzheimer's Disease

Amyloid plaque deposition starts at approximately 6 weeks in the neocortex. Amyloid deposits in the hippocampus appear at 3-4 months, and in the striatum, thalamus and brainstem at 4-5 months. Phosphorylated tau-positive neuritic processes have been observed in the vicinity of all congophilic amyloid deposits, but no fibrillar tau inclusions are seen.

Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months. Impaired reversal learning of a food-rewarded four-arm spatial maze task at 8 months.

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APP+PS1

Observed

X
Plaques at 76

Abundant plaques in hippocampus and subiculum, scattered plaques in cortex.
X
Neuronal Loss at 76

Necrotic neurons in hippocampus and cortex.
X
Cognitive Impairment at 40

Deficits in Barnes maze at 10 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), APP V717F (Indiana), PSEN1 L166P	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age.	Deficits in Barnes maze by 10 months of age.

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APP/PS1/rTg21221

Observed

X
Plaques at 35

Cortical plaques observed between 8-10 months. Plaques larger than in control mice not expressing human tau.
X
Neuronal Loss at 36

Neuronal loss observed adjacent to plaques relative to more distal areas.
X
Gliosis at 37

Increased astrocytosis adjacent to plaques relative to more distal areas.
X
Synaptic Loss at 40

Decreased synapse density adjacent to plaques relative to more distal areas.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1, MAPT	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic; MAPT: Transgenic	Alzheimer's Disease	Tau accumulations, dystrophic neurites, astrocytosis, neuronal loss, and synapse loss were more pronounced adjacent to cortical plaques. Tangles were not observed.	No data.

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AppSAA Knock-in

Observed

X
Plaques at 16

Amyloid plaques seen in App^SAA homozygous mice from 4 months of age and heterozygous mice at 16 months of age.
X
Gliosis at 16

Plaque-associated microgliosis observed by 4 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App	APP K670_M671delinsNL (Swedish), APP E693G (Arctic), APP T714I (Austrian)	App: Knock-In	Alzheimer's Disease	Homozygotes: Amyloid plaques and plaque-associated microgliosis from 4 months of age; cerebral amyloid angiopathy and dystrophic neurites from 8 months of age. Heterozygotes: Amyloid plaques at 16 months of age.	Unknown.

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APPsw/0; Pdgfrβ+/-

Observed

X
Plaques at 39

By 9 months of age APP^sw/0;Pdgfrβ^+/-mice have an elevated plaque load in the cortex and hippocampus compared with age matched APP^sw/0;Pdgfrβ^+/+.littermates. They also have extensive cerebral amyloid angiopathy.
X
Neuronal Loss at 39

Progressive neuronal degeneration including reduced neurite density and reduced neuronal number in the cortex and hippocampus of APP^sw/0; Pdgfrβ^+/-mice at at nine monthscompared to age-matched APP^sw/0; Pdgfrβ^+/+littermates.
X
Cognitive Impairment at 41

At nine months, APP^sw/0;Pdgfrβ^+/-mice perform poorly on several hippocampal-dependent behavioral tests including burrowing, nest construction, and novel object recognition, compared with age-matched APP^sw/0;Pdgfrβ^+/+littermates.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PDGFRB	APP K670_M671delinsNL (Swedish)	APP: Transgenic; PDGFRB: Knock-Out	Alzheimer's Disease	Amyloid plaques; elevated brain interstitial human and murine Aβ due to reduced clearance of soluble Aβ, cerebral amyloid angiopathy, tau hyperphosphorylation and related pathology. Neurite loss and neuronal loss in the cortex and hippocampus.	Age-associated cognitive impairment as measured by hippocampal-dependent tasks, including nest building, burrowing, and novel object recognition.

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APPSwDI x NOS2 Knock-out

Observed

X
Plaques at 49

Aβ deposits by 52 weeks. Particularly dense Aβ immunoreactivity in the subiculum and thalamus, including in the cerebral microvessels (Wilcock et al., 2008).
X
Tangles at 49

Extensive tau pathology by 52 weeks, including intraneuronal aggregates of hyperphosphorylated tau. Increased phosphorylated tau in bigenic mice compared to APPSwDI mice (Wilcock et al., 2008).
X
Neuronal Loss at 52

Significant neuron loss by 52 weeks in the hippocampus and subiculum, especially of neuropeptide Y neurons. Numerous Fluoro-Jade C+ neurons: 30% loss in the hippocampus, 35% loss in the subiculum (Wilcock et al., 2008).
X
Cognitive Impairment at 53

Impairments in spatial memory by 52-56 weeks as measured by the radial arm maze and the Barnes maze. Bigenic mice more impaired than APPSwDI (Wilcock et al., 2008).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, NOS2	APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa)	APP: Transgenic; NOS2: Knock-Out	Alzheimer's Disease	Plaques especially in the thalamus and subiculum. Aggregated, hyperphosphorylated tau tangles. Neuronal loss especially of NPY neurons in the hippocampus and subiculum. More severe pathology than Tg-SwDI alone.	Severe learning and memory deficits. Impaired spatial memory compared to Tg-SwDI as measured by the radial arm maze and the Barnes maze at 52-56 weeks.

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APP(Swedish) (R1.40)

Observed

X
Plaques at 59

By 13.5 months homozygous mice develop both parenchymal and vascular amyloid deposits which first appear in the frontal cortex. No Aβ deposition at 5 months (Lehman et al., 2003).
X
Gliosis at 61

Reactive astrocytes and microglia in 14-16 month old animals (Kulnane et al., 2001).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish)	APP: Transgenic	Alzheimer's Disease	By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months.	Unknown.

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APPSwe (line C3-3)

Observed

X
Plaques at 104

Some plaque formation at advanced age (24-26 months) (Savonenko et al., 2003).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish)	APP: Transgenic	Alzheimer's Disease	Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age.	Congenic animals showed normal reference and working memory up to 12-14 months.

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APPSwe/PSEN1(A246E)

Observed

X
Plaques at 39

By 9 months of age, amyloid plaques develop in the hippocampus and subiculum, later extending to the cortex (Borchelt et al., 1997). The striatum and thalamus are relatively spared out to 18 months of age. Amyloid pathology is more severe in female mice, with a greater amyloid burden measured at 12 and 17 months of age (Wang et al., 2003).
X
Gliosis at 52

By one year of age, reactive gliosis is observed in the cortex and hippocampus and is associated with dystrophic neurites (Borchelt et al., 1997).
X
Cognitive Impairment at 48

Age-associated cognitive impairment, as measured by the Morris water maze, was observed in 11 to 12-month-old males. Both acquisition and retention were impaired. No impairment at 3-4 months of age. At both time points mice performed normally on a position discrimination task in the T-maze (Puoliväli et al., 2002).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 A246E	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques by 9 months, starting in the hippocampus and subiculum. Plaques later develop in the cortex; the striatum and thalamus are relatively spared. Amyloid pathology is more severe in females. Dystrophic neurites and gliosis in the cortex and hippocampus.	Poor nest building. Reduced retention in a learned passive avoidance task. Increased immobility time in forced swim task. Age-associated impairment in acquisition and retention in the Morris water maze. No impairment in a position discrimination T-maze task.

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APPSwe/PSEN1dE9 (C3-3 x S-9)

Observed

X
Plaques at 26

Plaques are present in the hippocampus and cortex by 6 months of age.
X
Cognitive Impairment at 78

Age-related cognitive deficits. Episodic memory appears to be more sensitive than reference memory. No differences at 6 months of age, but detectable at 18 months (Savonenko et al., 2005).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Elevated Aβ42 and plaques in the hippocampus and cortex. No tangles. Reduced cholinergic markers.	Age-related cognitive deficits; episodic memory more sensitive than reference memory. No differences at 6 months, but detectable at 18 months.

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APPswe/PSEN1dE9 (C57BL6)

Observed

X
Plaques at 16

Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months.
X
Gliosis at 17

Plaque-associated astrogliosis and microgliosis are evident by 4 and 8 months, respectively.
X
Synaptic Loss at 18

Synapse loss in the hippocampus occurs by 4 months.
X
Cognitive Impairment at 40

Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques begin to emerge in the cortex at about 4 months of age and in the hippocampus at about 6 months. Gliosis and dystrophic neurites are associated with plaques. Amyloid angiopathy has been observed in the retina.	Hyperactivity is apparent by 6 months. Deficits in the Morris water maze emerge between 6 and 10 months and worsen with age.

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APPswe/PSEN1dE9 (line 85)

Observed

X
Plaques at 26

Occasional Aβ deposits can be found by 6 months, with abundant plaques in the hippocampus and cortex by 9 months (Jankowsky et al., 2004) and a progressive increase in plaques up to 12 months (Garcia-Alloza et al., 2006).
X
Neuronal Loss at 35

Neuronal loss observed adjacent to plaques relative to more distal areas.
X
Gliosis at 26

Minimal astrocytosis at 3 months; significant astrocytosis by 6 months, especially in areas around plaques. Extensive GFAP+ staining at 15 months and later throughout the cortex (Kamphuis et al., 2012).
X
Synaptic Loss at 17

In the B6 congenic mice, age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and Homer immunoreactivity in the hippocampus by 4 months (Hong et al., 2016).
X
Changes in LTP/LTD at 13

Transient long-term potentiation (t-LTP) is reduced by 3 months. The degree of impairment is not related to age from 3 to 12 months (Volianskis et al., 2008).
X
Cognitive Impairment at 52

Impairment in the Morris water maze at 12 months, specifically during acquisition of the hidden platform sub-task and the probe trial, but not in the visible platform test (Lalonde et al., 2005). At 13 months the mice commit more errors in the Morris water maze, but not at 7 months (Volianskis et al., 2008).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Occasional Aβ deposits by 6 months with abundant plaques in the hippocampus and cortex by 9 months and a progressive increase in plaques up to 12 months. No tangles. Decrease in synaptic markers and increase in complement immunoreactivity.	Cognitive impairment (e.g., deficits in spatial memory and contextual memory). Changes in spontaneous behavior (e.g., nest-building, burrowing).

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APP(V642I)KI

Observed

X
Cognitive Impairment at 117
Impairments at the water finding task at age 27-29 months, a test of long-term memory. No differences in the open field test of the elevated plus maze indicating no difference in general behavioral patterns, activity level, or emotional state.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP V717I (London)	APP: Transgenic	Alzheimer's Disease	Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy.	At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels.

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APP(V717I)

Observed

X
Plaques at 43

Plaques start in the cortex and subiculum at ~10 months. Diffuse amyloid deposits and compact neuritic plaques at 13-18 months especially in the hippocampus and cortex, with occasional deposits in the thalamus and fimbria, external capsule, pontine nuclei, and white matter (Moechars et al., 1999). Prominent amyloid deposits in brain vessels after 15 months (Van Dorpe et al, 2000).
X
Gliosis at 43

GFAP, microglial activation, and other markers of brain inflammation are elevated by 10 months.
X
Changes in LTP/LTD at 26

Significant deficit in LTP in CA1 region of the hippocampus at 6 months.
X
Cognitive Impairment at 26

From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze and other tests. Also deficits in associative learning.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP V717I (London)	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.	From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression.

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APP(V717I) x PS1(A246E)

Observed

X
Plaques at 17

Plaques start in cortex, hippocampus and subiculum at 4-6 months.
X
Gliosis at 20

Elevated GFAP, microglial activation, and other markers of brain inflammation increase as of 4.5 months.
X
Changes in LTP/LTD at 26

Significant deficit in LTP in CA1 region of the hippocampus at 6 months.
X
Cognitive Impairment at 22

From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris water maze and other tests. Also deficits in associative learning.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP V717I (London), PSEN1 A246E	APP: Multi-transgene; PSEN1: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Soluble, oligomeric Aβ at 2 months and increases with age. Amyloid plaques at 6-9 months, earlier than APP(V717I) single transgenics. Plaques start in the subiculum and spread to the frontal cortex. Amyloid-associated inflammation. CAA pathology at 8 months; microbleeds at 12-15 months. Dystropic neurites containing hyperphosphorylated tau, but no tangle pathology.	From the age of 5 months, spatial and non-spatial orientation and memory deficits by Morris Water Maze. Impaired associative learning, hyperactivity, anxiety, and aggression.

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Arc48 (APPSw/Ind/Arc)

Observed

X
Plaques at 9

Parenchymal neuritic plaques by 2 months with prominent plaque deposition in the hippocampus by 3-4 months. Abundant mature thioflavin-S positive plaques with dystrophic neurites by 10-12 months (Cheng et al., 2007).
X
Gliosis at 13

Reactive astrocytosis at 3-4 months in the dentate gyrus as demonstrated by GFAP immunoreactivity (Cheng et al., 2007).
X
Cognitive Impairment at 13

At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but were impaired in the ability to use extramaze cues to navigate to the hidden platform (Cheng et al., 2007).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana), APP E693G (Arctic)	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20.	At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform.

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ArcAβ

Observed

X
Plaques at 39

Between 9 and 15 months of age β-amyloid plaques became prominent. Plaques had a characteristic dense core morphology which differed from the cotton wool-like structure of plaques seen with the Swedish mutation alone (Knobloch et al., 2007).
X
Changes in LTP/LTD at 15

LTP is severely impaired in slices from 3.5 and 7.5 month old mice. LTP and basal synaptic transmission were normal in slices from one month old mice (Knobloch et al., 2007).
X
Cognitive Impairment at 26
Cognitive impairment measured from the age of 6 months in the Morris water maze and Y-maze, as well as in active avoidance behavior (Knobloch et al., 2007).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP E693G (Arctic)	APP: Transgenic	Alzheimer's Disease	At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma.	Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze.

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ARTE10

Observed

X
Plaques at 13

Robust and reliable plaque pathology as early as 3 months in homozygotes, 5 months in hemizygotes. Plaques start in the anterior neocortex and subiculum, spreading to other brain regions (e.g. hippocampus, thalamus, amygdala). Congophilic dense-core plaques are abundant, with lower levels of diffuse plaques and some cerebral amyloid angiopathy.
X
Gliosis at 22

Glial activation, including reactive astrocytes and activated microglia, is present in areas around plaques by 5 months of age in homozygous animals, later in hemizygotes.
X
Synaptic Loss at 13

Decreased expression of synaptophysin mRNA in the brain by 3-4 months of age in both hemizygous and homozygous animals.
X
Cognitive Impairment at 52

Select, paradigm-dependent, deficits in learning and memory, especially episodic memory, by 12 months in homozygous and hemizygous mice.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 M146V	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Robust early plaque development (by 3 months in homozygotes, 5 months in hemizygotes), predominantly congophilic dense-core amyloid plaques surrounded by dystrophic neurites and gliosis. Some diffuse plaques and cerebral amyloidosis. No tau tangles. Neurons have reduced dendritic length, surface area, and branches.	Age-related learning and memory deficits, especially episodic memory, in select paradigm-specific tasks by 12 months.

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Atg16LΔWD

Observed

X
Neuronal Loss at 104

Apparent neuron loss in hippocampi of 2-year-old mice (fewer neurons, increased levels of cleaved caspase-3, and increased numbers of TUNEL-positive neurons).
X
Gliosis at 104

Microgliosis in the hippocampi of 2-year-old mice.
X
Changes in LTP/LTD at 104

Impaired long-term potentiation at CA3-CA1 synapses.
X
Cognitive Impairment at 104

Deficits in the sucrose preference test, spontaneous alternation in the Y-maze, and novel object recognition test.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Atg16l1		Atg16l1: Knock-Out	Alzheimer's Disease	Intracellular and extracellular Aβ deposits, but no dense-core plaques. Microgliosis and neuron loss in 2-year-old mice.	Deficits in the sucrose-preference test, spontaneous alternation in the Y-maze, and novel object recognition test.

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BACE1 cKO (Hu, Yan) X 5xFAD

Observed

X
Plaques at 11

Accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.
X
Gliosis at 11

Reactive astrocytes and microglia accumulate up to day 120, but to a lesser degree than in control 5xFAD, then recede thereafter.
X
Changes in LTP/LTD at 40

Deficit in LTP at Schaffer collateral–CA1 synapses, but less severe than in control 5xFAD mice.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Bace1, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Bace1: Conditional Knock-out; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, reactive astrocytes and microglia, and dystrophic neurites accumulate up to day 120, but to a lesser degree than in control 5xFAD (5xFAD mice homozygous for a floxed Bace1 gene), then recede thereafter.	Normal contextual and cued fear conditioning, tested at 8 to 10 months of age.

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Bace1 conditional knock-out (adult, whole body) (Vassar)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Bace1		Bace1: Conditional Knock-out	Alzheimer's Disease	Defects in axonal organization.	Normal learning and memory in the Morris water maze, normal alternation in the Y-maze test of working memory, and normal cued and contextual fear conditioning; possible hyperactivity in novel situations.

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BACE1 conditional knock-out (Hu, Yan)

Observed

X
Changes in LTP/LTD at 40

Long-term potentiation at Schaffer collateral–CA1 synapses impaired in slices obtained from 10- to 12-month-old mice.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Bace1		Bace1: Conditional Knock-out	Alzheimer's Disease	No gross morphological changes observed.	BACE1-deficient mice and Bace1^fl/fl mice performed similarly in tests of contextual and cued fear conditioning at 8 to 10 months of age.

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Bace1 conditional knock-out (neonatal, forebrain) (Vassar)

Observed

X
Cognitive Impairment at 24

Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Bace1		Bace1: Conditional Knock-out	Alzheimer's Disease	Hypomyelination and defects in axon organization.	Delayed learning, but normal memory, in the Morris water maze; normal alternation in the Y-maze test of working memory, normal cued and contextual fear conditioning. Hyperactivity in when placed in novel environments.

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Bace1 conditional knockout (Tesco)

Observed

X
Changes in LTP/LTD at 60

Deficit in long-term potentiation at Schaffer collateral–CA1 synapses in slices from 14-month-old animals that had received tamoxifen between 8 and 12 weeks of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Bace1		Bace1: Conditional Knock-out	Alzheimer's Disease	None observed: hippocampal mossy fiber organization and sciatic-nerve myelination were normal.	Performed similarly to controls in a battery of tests (Y-maze, contextual fear conditioning, pre-pulse inhibition, open field, and light-dark transition task).

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BRI-Aβ42 (BRI2-Aβ42)

Observed

X
Plaques at 13

Detergent-insoluble amyloid-β and cored plaques as early as three months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices by 12 months. Extensive congophillic amyloid angiopathy.
X
Gliosis at 13

Plaque-associated reactive gliosis as measured by GFAP immunostaining.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
		Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss.	On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.

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CAST.APP/PS1

Observed

X
Plaques at 32

Thioflavin S-positive amyloid plaques are present in the cortex and hippocampus by 8 months of age, with more severe plaque pathology in females than in males.
X
Neuronal Loss at 34

Compared with their non-transgenic littermates, CAST.APP/PS1 mice have fewer neurons in area CA1 of the hippocampus. Cortical neuron numbers do not differ between the genotypes.
X
Gliosis at 33

Plaque-associated microgliosis observed by 8 months.
X
Cognitive Impairment at 31

Deficits in short-term memory by 8 months in males (data from females unavailable).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in hippocampal area CA1.	Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in males (data from females is not available, as wild-type females are unable to perform this test).

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Ceacam1 KO/APOE4/Trem2*R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, Ceacam1, Trem2	TREM2 R47H	APOE: Knock-In; Ceacam1: Knock-Out; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Clasp2L163P/APOE4/Trem2R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Clasp2, APOE, Trem2	TREM2 R47H	Clasp2: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Dp(16)1Yey/+

Observed

X
Neuronal Loss at 56

Loss of vulnerable neurons (neurons in layer II of entorhinal cortex, catecholaminergic neurons in the locus coeruleus and the basal forebrain at advanced ages.
X
Synaptic Loss at 37

Critical synaptic proteins were altered, including syntaxin 1A and SNAP25.
X
Changes in LTP/LTD at 8

Magnitude of hippocampal LTP following theta burst stimulation is lower than the WT controls around 2-4 months of age.
X
Cognitive Impairment at 9

Cognitive impairments were observed at 2-4 months of age, as well as at more advanced ages.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
		Multi-transgene	Down's Syndrome, Alzheimer's Disease	Neuronal loss in the entorhinal cortex, locus coeruleus, and the basal forebrain magnocellular complex; increased tau pathology and increased astrocyte and microglia levels.	Impairments in contextual memory, spatial learning, novel object recognition memory, and vocalizations.

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Dp1Tyb

Observed

X
Gliosis at 14

Increased density of microglia in the hippocampus at 14 weeks of age.
X
Cognitive Impairment at 8

Exploratory behavior is impaired at 8 weeks of age. Fear memory is impaired at 10 months. Spatial working memory is impaired at 3-months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
		Knock-In	Down's Syndrome, Alzheimer's Disease	No amyloid plaques. At 14 weeks, smaller and rounder brain, reduced medial prefrontal cortex and dorsal hippocampus volumes, reduced density of neurons, and increased density of microglia in the hippocampus. Altered hippocampal metabolites including glutamine and the glutamine/glutamate ratio. Reduced IB4 neurons in the DRG.	Exploratory behavior is impaired at 8 weeks of age. Fear memory is impaired at 10 months. Motor function is impaired at 12-15 weeks of age. Sleep architecture is disrupted at 16-weeks of age. Spatial working memory is impaired at 3-months of age.

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Dp9Tyb

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
			Down's Syndrome, Alzheimer's Disease	Unknown.	No locomotor defects as assessed by Rotarod at 12 weeks of age.

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E2FAD

Observed

X
Plaques at 17

Plaques develop in the subiculum and deep cortical layers by 4 months.
X
Gliosis at 26

Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
X
Synaptic Loss at 17

Protein levels of NMDA receptor subunits decreased from 2 to 6 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.	In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice.

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E3FAD

Observed

X
Plaques at 17

Plaques develop in the subiculum and deep cortical layers by 4 months.
X
Gliosis at 26

Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
X
Synaptic Loss at 17

Protein levels of NMDA receptor subunits decreased from 2 to 6 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.	In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice.

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E4FAD

Observed

X
Plaques at 17

Plaques develop in the subiculum and deep cortical layers by 4 months.
X
Gliosis at 26

Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
X
Synaptic Loss at 17

Decreased protein levels of PSD95 and NMDA receptor subunits by 4 months.
X
Cognitive Impairment at 8

Modest learning deficits in the Morris water maze by 2 months. Progressive decrease in performance on learning and memory tasks.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins.	Age-dependent learning and memory deficits in the Y maze and Morris water maze.

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hAbeta/APOE4/Trem2*R47H (LOAD2)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, APP, Trem2	TREM2 R47H	APOE: Knock-In; APP: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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hAbeta-loxP-KI

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP		APP: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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hAβ-KI

Observed

X
Synaptic Loss at 78

Fewer synaptophysin-immunoreactive puncta, but similar numbers of PSD95-immunoreactive puncta, in knock-in mice compared with wild-type mice.
X
Changes in LTP/LTD at 78

Impaired theta-burst-induced LTP at Schaffer collateral-CA1 synapses, by 18 months of age.
X
Cognitive Impairment at 40

Differed from wild-type mice in the contextual fear conditioning test by 10 months of age and in the novel object recognition task by 14 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
App		App: Knock-In	Alzheimer's Disease	No amyloid plaques observed through 22 months of age. Accelerated formation of OC-immunoreactive and Periodic Acid Schiff-positive granules.	Differed from wild-type mice in the contextual fear conditioning test by 10 months of age and in the novel object recognition task by 14 months.

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hCR1 KI on APOE4/Trem2

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Cr2, CR1, CR2, APOE, Trem2	TREM2 R47H	Cr2: Knock-Out; CR1: Knock-In; CR2: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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htau

Observed

X
Tangles at 39

Aggregated tau and paired helical filaments detectable at nine months by immunoelectron microscopy, although paired helical filaments of aggregated insoluble tau can be isolated from brain tissue as early as two months. Tau first redistributes from axons to cell bodies. Hyperphosphorylated tau begins to accumulate by six months, and increases further by 13 and 15 months (Andorfer et al., 2003).
X
Neuronal Loss at 43

Decrease in cortical thickness and reduced cell number between 10 and 14 months of age. Increased ventricle size increased from age eight months to 18 months. Decrease in the thickness of the corpus callosum (Andorfer et al., 2005).
X
Changes in LTP/LTD at 52

In hippocampal slices, LTP induced by high frequency stimulation (HFS) was normal at four months but abolished by 12 months. LTP induced by theta burst stimulation (TBS) was normal at both ages. Paired-pulse ratio (PPR) was unaffected at four months, but increased at 12 months compared with controls, suggesting a decrease in probability of transmitter release (Polydoro et al., 2009).
X
Cognitive Impairment at 26

Abnormal spatial learning in six-month-old mice compared with control mice (Phillips et al., 2011). Normal object recognition and spatial learning and memory by MWM at four months, but deficits by 12 months (Polydoro et al., 2009). Impaired burrowing relative to control mice occurs by four months (Geiszler et al., 2016).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT		MAPT: Knock-Out; MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Age-associated tau pathology, including redistribution of tau to cell bodies and dendrites, phosphorylated tau, accumulation of aggregated paired helical filaments, and ultimately thioflavin-S positive neurofibrillary tangles. Pathology most severe in neocortex and hippocampus, and minimal in the brain stem and spinal cord. Some neuronal loss.	Normal object-recognition memory and spatial learning/memory (as assessed by the Morris Water Maze) at four months, but impaired at 12 months (Polydoro et al., 2009).

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hTau-A152T

Observed

X
Neuronal Loss at 87

Neuron loss in the hippocampus was observed by 20 months.
X
Gliosis at 17

Astrocytosis, but no differences in microglia.
X
Cognitive Impairment at 74

In the Morris water maze, performance was impaired after 17 months of age. Nest building was impaired at 10-14 months. Social interaction, anxiety, exploratory behavior, and motor functions were unaltered.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT A152T	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Tangles or dense tau inclusions not observed. Abnormal accumulations of soluble tau. Age-dependent neuronal loss was observed in the hippocampus.	Age-dependent learning and memory deficits in the Morris water maze. Nest building impaired. Social interaction, anxiety, exploratory behavior, and motor functions were normal.

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hTau-AT (hTau40-AT)

Observed

X
Tangles at 13

Tangles in hippocampus, cortex, and spinal cord starting at 3 months with age-dependent increases. Hyperphosphorylation, conformation changes, and mislocalization.
X
Neuronal Loss at 52

Neuron loss in the hippocampus and cortex at 12 months.
X
Gliosis at 43

Astrocytosis and microgliosis at 10 months.
X
Synaptic Loss at 87

Synaptophysin, but not PSD95, decreased in hippocampus and cortex at 12 months. By Golgi staining, spines unchanged in CA1 at 10 months, increased in CA3 at 12 months, and decreased in CA1 and CA3 at 16 months.
X
Cognitive Impairment at 70

No change at 10 months but at 16 months deficits in learning and memory (Morris water maze).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT A152T	MAPT: Knock-In	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Tangles in hippocampus, cortex, and spinal cord at 3 months with age-dependent increases. Tau hyperphosphorylation, conformation changes, and mislocalization observed. Age-dependent loss of synapses.	Age-dependent learning and memory deficits in the Morris water maze. Motor functions normal.

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hTau.P301S

Observed

X
Tangles at 17

Neurofibrillary tangles detected as early as 4 months of age.
X
Neuronal Loss at 13

Neuronal loss starting at 3 months. Loss is especially prominent in the spinal cord with notable loss of superficial cortical neurons as well (Hampton et al., 2010).
X
Gliosis at 22

Astrocytosis, as measured by GFAP reactivity, in 6 month-old animals. Microglial activation in the brain stem and spinal cord of 5 month-old animals by OX42 staining (Bellucci et al., 2004).
X
Cognitive Impairment at 11

Memory deficit starting at 2.5 months as assessed by the Morris water maze (Xu et al., 2014), but no deficit at 2 months (Scattoni et al., 2010).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT P301S	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis.	Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months.

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hTREM2-KI

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
TREM2		TREM2: Knock-In	Alzheimer's Disease

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hTREM2-R47H_KI

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
TREM2	TREM2 R47H	TREM2: Knock-In	Alzheimer's Disease

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Il1rap KO/APOE4/Trem2*R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, Il1rap, Trem2	TREM2 R47H	APOE: Knock-In; Il1rap: Knock-Out; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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J20 (PDGF-APPSw,Ind)

Observed

X
Plaques at 22

At 5-7 months of age diffuse amyloid-β plaques deposit in the dentate gyrus and neocortex. Amyloid deposition is progressive with widespread plaques by 8-10 months. Aβ puncta are deposited in the hippocampus as early as 1 month (Hong et al., 2016).
X
Neuronal Loss at 12

Cell loss varies by brain region. No significant neuronal loss was observed in the CA3 region of the hippocampus at 6, 12, 24 and 36 weeks of age nor in the CA1 region at 6 weeks; however, at 12, 24, and 36 weeks significant neuronal loss was observed in the CA1 region compared to age-matched wild-type animals (Wright et al., 2013).
X
Gliosis at 24

At 24 and 36 weeks a significant increase in the number of reactive GFAP+ astrocytes and CD68+ microglia was observed in the hippocampi of J20 mice compared to age-matched wild-type controls. No significant difference was observed at 6 and 12 weeks (Wright et al., 2013).
X
Synaptic Loss at 15

Age-dependent loss of synaptophysin, synaptotagmin, PSD-95, and homer immunoreactivity in the hippocampus by 3 months; synapse loss was confirmed by electron microscopy. No significant difference was seen at 1 month (Hong et al., 2016).
X
Changes in LTP/LTD at 13

Basal synaptic transmission is impaired between 3-6 months; extracellularly recorded field EPSPs at the Schaffer collateral to CA1 synapse in acute hippocampal slices were on average smaller in amplitude than those seen in wild-type mice. Significant deficits in LTP at the Schaffer collateral–CA1 synapse compared with control mice at 3-6 months (Saganich et al., 2006).
X
Cognitive Impairment at 16

Deficits in spatial memory and learning appear as the mice age. By 4 months, J20 mice demonstrate spatial reference memory deficits as measured by the radial arm maze (Wright et al., 2013) and Morris water maze (Cheng et al., 2007).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	APP: Transgenic	Alzheimer's Disease	Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptic markers and increase in complement immunoreactvity.	Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated.

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JNPL3(P301L)

Observed

X
Tangles at 20

Neurofibrillary tangles develop in an age and gene-dose dependent manner; as early as 4.5 months in homozygotes and 6.5 months in heterozygotes. Tangles and Pick-body-like neuronal inclusions in the amygdala, septal nuclei, preoptic nuclei, hypothalamus, midbrain, pons, medulla, deep cerebellar nuclei and spinal cord (Lewis et al., 2000).
X
Neuronal Loss at 43

Neuronal loss, especially in the spinal cord, most prominent in the anterior horn (Lewis et al., 2000).
X
Gliosis at 43

Astrogliosis (as measured by GFAP reactivity) in brainstem, diencephalon, and basal telencephalon by 10 months (Lewis et al., 2000).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT P301L	MAPT: Transgenic	Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease	Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord.	By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization.

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Kif21bT82T/APOE4/Trem2R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Kif21b, APOE, Trem2	TREM2 R47H	Kif21b: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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MAPT(H1.0)-GR

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT, MAPT-AS1, Mapt		MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Unknown.	Unknown.

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MAPT(H2.1)-GR

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT, MAPT-AS1, Mapt		MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Unknown.	Unknown.

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MAPT knock-in

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT		MAPT: Knock-In	Alzheimer's Disease, Other Tauopathy	No evidence of increased neuroinflammation, neuronal death, or brain atrophy in MAPT knock-in mice, compared with wild-type mice.	MAPT knock-in mice perform similarly to wild-type mice in the Y-maze test of working memory.

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McGill-R-Thy1-APP

Observed

X
Plaques at 24

Amyloid plaques present in homozygotes, appearing in hippocampus at 6 months and cortex at 13 months. Plaques are generally absent in hemizygotes.
X
Neuronal Loss at 72

A 22 percent reduction in the number of neurons was seen in the subiculum of homozygous transgenic rats at 18 months.
X
Gliosis at 24

Microgliosis and astrogliosis observed in homozyogotes.
X
Synaptic Loss at 80

Reduction in cholinergic synaptic boutons seen at 20 months in homozygous transgenic rats.
X
Changes in LTP/LTD at 14

Impairments in long-term potentiation in CA1 by 3.5 months of age.
X
Cognitive Impairment at 12

Deficits in Morris water maze and fear conditioning test are apparent by 3 months of age in both hemizygous and homozygous transgenic rats.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	APP: Transgenic	Alzheimer's Disease	Hemizygotes: intraneuronal Aβ in hippocampus and cortex by one week, but no plaques even at advanced ages. Homozygotes: intraneuronal Aβ in hippocampus and cortex by one week; amyloid plaques in hippocampus beginning at 6 months, in cortex beginning at 13 months.	Cognitive deficits are apparent by three months of age in both hemizygous and homozygous transgenic rats.

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MthfrC677T/APOE4/Trem2R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Mthfr, APOE, Trem2	TREM2 R47H	Mthfr: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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mThy-1 3R Tau (line 13)

Observed

X
Tangles at 34

Pick-body like inclusions of aggregated tau appeared in the hippocampus and cortex by 8-10 months. Inclusions were positive for Bielchowsky silver stain but negative for Gallyas-silver stain and Thioflavin-S.
X
Neuronal Loss at 34

Neuronal loss occurred by 8-10 months as evidenced by decreased NeuN staining in the dentate gyrus and CA3 regions of the hippocampus. Neocortical volume also decreased.
X
Gliosis at 35

Astrogliosis was seen by 8-10 months in the neocortex and hippocampus. Some GFAP+ astrocytes also contained 3R tau.
X
Cognitive Impairment at 26

By 6-8 months memory impairment was evident as a failure to habituate to a novel environment. This deficit was not present at 3-4 months. At 8-10 months, transgenics also took longer than wild-type mice to find the hidden platform in the Morris water maze.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT L266V, MAPT G272V	MAPT: Transgenic	Frontotemporal Dementia, Pick's disease, Alzheimer's Disease	Accumulation of 3R tau in neurons of the cortex and hippocampus. Pick body-like tau aggregates and neuronal loss in the hippocampus and cortex. Astrogliosis, with some 3R tau in GFAP-positive astrocytes. Synapto-dendritic changes and mitochondrial pathology.	Age-related memory and motor deficits as assessed by habituation to a novel environment, the Morris water maze, and the round beam test.

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mThy1-hAPP751 (TASD41)

Observed

X
Plaques at 13

Plaques start at 3-6 months in the frontal cortex and become widespread with age, affecting the piriform and olfactory cortices, hippocampus, and thalamus (Rockenstein et al., 2001; Havas et al., 2011).
X
Gliosis at 27

Inflammation related to activated microglia (increased CD11) and reactive astrocytes (increased GFAP) is significant by 6 months and increases with age.
X
Synaptic Loss at 52

Dystrophic neurites and synaptic loss starting at 12 months.
X
Cognitive Impairment at 26

Cognitive impairment observed by 6 months by Morris Water Maze (Rockenstein et al., 2005).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP V717I (London)	APP: Transgenic	Alzheimer's Disease	Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region.	Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration.

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NSE-APP751

Observed

X
Plaques at 8

Aβ deposits were observed as early as two months of age. These deposits were diffuse and extracellular and had a “cotton-like” appearance. Classic mature plaques were not observed.
X
Gliosis at 95

Gliosis was noted in a single 22-month-old animal with extensive Aβ deposits (Higgins et al., 1994).
X
Cognitive Impairment at 52

Deficits in spatial memory and learning appear as the mice age. At 12 months the mice demonstrate learning and memory deficits as measured by a water-maze task and in spontaneous alternation in a Y maze (Moran et al., 1995). At six months cognition is largely normal.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP		APP: Transgenic	Alzheimer's Disease	Age-dependent increase in Aβ deposits and tau immunoreactivity.	Learning and memory deficits are age-dependent as assessed on spontaneous alternation in a Y maze and in the water-maze task.

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PA-Rab5

Observed

X
Neuronal Loss at 28

Loss of basal forebrain cholinergic neurons, beginning at 7 months.
X
Synaptic Loss at 34

Loss of spines in CA3 and dentate gyrus regions of the hippocampus, observed in 8.5-month-old mice.
X
Changes in LTP/LTD at 24

Pronounced defect in LTD and slight impairment in LTD at Schaffer collateral-CA1 synapses in hippocampal slices from 6-month-old mice.
X
Cognitive Impairment at 24

When tested at 6 months of age, the performance of PA-Rab5 mice differed from wild-type controls in a novel object recognition test.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
RAB5A		RAB5A: Transgenic	Alzheimer's Disease	Enlarged Rab5-positive endosomes, tau hyperphosphorylation, synapse loss in hippocampus, and loss of basal forebrain cholinergic neurons.	When tested at 6 months of age, the performance of PA-Rab5 mice differed from wild-type controls in a novel object recognition test.

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PDAPP(line109)

Observed

X
Plaques at 26

In heterozygous mice no plaque pathology at 4-6 months. At 6-9 months mice begin to exhibit deposits of human Aβ in the hippocampus, corpus callosum, and cerebral cortex. Plaques become more extensive with age and vary in size and structure including diffuse irregular plaques and compact cored plaques (Games et al., 1995).
X
Gliosis at 26

GFAP-positive astrocytes and activated microglia associated with plaques (Games et al., 1995).
X
Synaptic Loss at 35

Decreased synaptic density in the dentate gyrus as measured by synaptophysin immunoreactivity. Also decreased dendritic density as measured by MAP2 immunoreactivity (Games et al., 1995).
X
Changes in LTP/LTD at 17

Alterations in LTP induced by theta burst stimulation at 4-5 months which is prior to plaque formation; although the potentiation immediately after TBS was comparable to control mice, the potentiation decayed more rapidly in PDAPP mice. Also paired pulse facilitation was enhanced. Responses to high frequency stimulation bursts were distorted (Larson et al., 1999).
X
Cognitive Impairment at 13

Deficits in a variety of memory paradigms from a young age. Robust deficits in the radial arm maze at 3 months (deficits appear before amyloid plaque deposits). Object recognition, 6, 9-10 months. Operant learning, 3, 6 months (Dodart et al., 1999).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP V717F (Indiana)	APP: Transgenic	Alzheimer's Disease	Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus.	Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months.

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PDGF-APP(WT) (line I5)

Observed

X
Synaptic Loss at 9

By 2-4 months of age, there is a decrease in synaptophysin-immunoreactive presynaptic terminals compared to nonTg controls. Synaptophysin immunoreactivity decreases further with age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP		APP: Transgenic	Alzheimer's Disease	Expression of human APP in the brain especially in the neocortex and hippocampus. No plaques up to 24 months.	Unknown.

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PLB1-triple (hAPP/hTau/hPS1)

Observed

X
Gliosis at 52

Increased inflammation (GFAP labelling) detected at 12 months in cortex and hippocampus (Platt, unpublished observation).
X
Changes in LTP/LTD at 26

Impairments in long-term and short-term hippocampal plasticity. LTP following theta-burst stimulation decayed faster and paired-pulse facilitation was reduced relative to wild-type mice at both six and 12 months of age. Synaptic transmission impacted at 12 months.
X
Cognitive Impairment at 22

Social recognition memory was impaired by five months and further impaired by 12 months. Similarly, object recognition memory was impaired by eight months. Spatial learning impairments were seen later; at 12 months deficits in spatial acquisition learning were seen in the open field water maze that were not apparent at 5 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, MAPT, PSEN1	APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W	APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene	Alzheimer's Disease	Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT.	Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity.

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PLB4 (hBACE1)

Observed

X
Gliosis at 52

Increased GFAP-positive astrocytes at 12 months of age in the dentate gyrus, CA1 region of the hippocampus, and the piriform cortex. Gliosis is suspected to begin earlier than 12 months.
X
Cognitive Impairment at 13

Impaired spatial representation in a habituation task by 3 months of age. By 6 months, impaired learning and memory by a variety of tasks including the Y-maze, Morris water maze, and a test of the social transmission of food preference. These effects appear to be distinct from reduced motor activity and reduced anxiety.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
BACE1		BACE1: Transgenic	Alzheimer's Disease	Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology.	Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety.

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Plcγ2-P522R knock-in

Observed

X
Gliosis at 24

Astrogliosis revealed by GFAP immunohistochemistry in 6-month-old males. Microglial activation revealed by TSPO PET imaging in year-old females.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Plcg2		Plcg2: Knock-In	Alzheimer's Disease, Dementia with Lewy Bodies, Frontotemporal Dementia	Hypertrophic astrocytes in the hippocampi, revealed by GFAP immunohistochemistry. Microglial activation revealed by TSPO PET imaging.	Unknown.

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Plcg2 KO

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Plcg2		Plcg2: Knock-Out	Alzheimer's Disease	Unknown.	Unknown.

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Plcg2M28L/APOE4/Trem2R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, Plcg2, Trem2	TREM2 R47H	APOE: Knock-In; Plcg2: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Plcg2*M28L x 5xFAD

Observed

X
Plaques at 30

Diffuse and compact amyloid plaques observed in mice studied at 7.5 months of age. Higher plaque burdens than 5xFAD.
X
Gliosis at 31

Microgliosis observed in mice studied at 7.5 months of age.
X
Synaptic Loss at 32

Decreased basal synaptic transmission, lower frequencies and amplitudes of spontaneous excitatory postsynaptic currents and spontaneous inhibitory postsynaptic currents recorded in hippocampal CA1 region, compared with wild-type mice.
X
Changes in LTP/LTD at 33

Impaired LTP at Schaffer collateral-CA1 synapses, compared with wild-type.
X
Cognitive Impairment at 24

Deficits in working memory (decreased spontaneous alternation in the Y-maze), compared with wild-type.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Plcg2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Plaque burdens in the cortex and subiculum were elevated in 5xFAD^M28L mice but microglia showed less interaction with plaques, compared with 5xFAD.	Six-month-old 5xFAD^M28L and 5xFAD mice showed similar deficits in working memory, assessed in the Y-maze.

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Plcg2*P522R

Observed

X
Gliosis at 24

Plcg2*P522R knock-in mice had a slightly higher density of Iba1-positive microglia than wild-type mice. Microglia in the knock-in animals were simpler in shape—with less ramified processes—and contained a greater density of puncta immunoreactive for the lysosomal marker CD68, compared with wild-type microglia.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Plcg2		Plcg2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Plcg2*P522R x 5xFAD

Observed

X
Plaques at 30

Diffuse and compact amyloid plaques observed in mice studied at 7.5 months of age. Lower plaque burdens than 5xFAD.
X
Gliosis at 31

Microgliosis observed in mice studied at 7.5 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Plcg2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Plcg2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Plaque burdens in the cortex and subiculum were lower in 5xFAD^P522R mice and microglia showed increased interaction with plaques, compared with 5xFAD.	The PLCγ2 P522R variant protected against deficits in the Y-maze test of working memory in 5xFAD mice.

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Plcg2*P522R x APP NL-G-F

Observed

X
Plaques at 24

ThioflavinS-positive amyloid plaques observed in mice studied at 6 months of age. Higher plaque burdens than APP^NL-G-F.
X
Gliosis at 24

Microgliosis observed in mice studied at 6 months of age. Attenuated microglia-plaque interactions in the hippocampus, compared with APP^NL-G-F.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Plcg2, App	APP K670_M671delinsNL (Swedish), APP I716F (Iberian), APP E693G (Arctic)	Plcg2: Knock-In; App: Knock-In	Alzheimer's Disease	Sex- and region-dependent increases in plaque burden, and decreases in microglia-plaque interactions, in Plcg2*P552R x APP^NL-G-F mice, compared with APP^NL-G-F.	Unknown.

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PS19 with humanized TREM2 (common variant)

Observed

X
Tangles at 37

Tangles revealed using antibody PG5 at 9 months.
X
Neuronal Loss at 38

At 9 months, atrophy of hippocampus and entorhinal/piriform cortex and pronounced ventricular expansion. Thinning of the granule cell layer of the dentate gyrus and pyramidal cell layer of the piriform cortex, compared with PS19 mice carrying TREM2-R47H.
X
Gliosis at 39

Elevated expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the R47H variant of TREM2.
X
Synaptic Loss at 40

Fewer synapses and more dystrophic synapses, compared with PS19 mice carrying the R47H variant of TREM2.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT, TREM2, Trem2	MAPT P301S	MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia	Brain atrophy by 9 months of age. Increased microgliosis, astrogliosis and synapse loss, compared with PS19 mice carrying TREM2 with the R47H mutation.	Not known.

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PS19 with humanized TREM2 (R47H)

Observed

X
Tangles at 36

Tangles revealed using antibody PG5 at 9 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT, TREM2, Trem2	MAPT P301S, TREM2 R47H	MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia	Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2.	Not known.

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PS1 conditional Knock-out

Observed

X
Cognitive Impairment at 22

Mild impairment of spatial learning and memory in the Morris water maze observed in 5 month-old mice (Yu et al., 2001).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
PSEN1		PSEN1: Conditional Knock-out	Alzheimer's Disease	Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments.	Subtle but significant deficits in long-term spatial memory in the Morris water maze.

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PS2APP

Observed

X
Plaques at 26

Age-associated development of plaques: none at 3 months, overt Aβ deposition at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months (Ozmen et al., 2009; Weidensteiner et al. 2009).
X
Gliosis at 26

Gliosis at 6 months (personal communication, Laurence Ozmen).
X
Changes in LTP/LTD at 43

A strong increase in LTP and post-tetanic potentiation induced by tetanic stimulation in hippocampal slices of 10 month-old animals compared to wild-type mice (Poirier et al., 2010).
X
Cognitive Impairment at 35

Cognitive impairment is detected by the Morris water maze (probe trial 2) at 8 and 12 months of age, not at 3 months (personal communication Laurence Ozmen).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN2	APP K670_M671delinsNL (Swedish), PSEN2 N141I (Volga)	APP: Transgenic; PSEN2: Transgenic	Alzheimer's Disease	Age-associated development of plaques: none at 3 months, overt Aβ deposition in the brain at approximately 6 months, with heavy plaque load in the hippocampus, frontal cortex, and subiculum at 10 months. Aβ deposits in blood vessels were sporadic, mainly in large vessels. Cerebral amyloid deposits correlate with levels of the human APP transcript at 12 months.	Cognitive impariment detected by the Morris water maze at 8 and 12 months of age, but not at 3 months.

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PS2APP (PS2(N141I) x APPswe)

Observed

X
Plaques at 39

Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution over time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei (Richards et al., 2003).
X
Gliosis at 39

An inflammatory response indicated by the presence of activated microglia and astrocytes begins around 9 months. The onset, distribution, and abundance of activated microglia and astrocytes correlate with Aβ deposition.
X
Cognitive Impairment at 35

Age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze (Richards et al., 2003).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN2	APP K670_M671delinsNL (Swedish), PSEN2 N141I (Volga)	APP: Transgenic; PSEN2: Transgenic	Alzheimer's Disease	Rare amyloid deposits at 5 months, with consistent deposits in the subiculum and frontolateral cortices by 9 months. Plaques increase in number and distribution with time, spreading throughout the neocortex and hippocampus as well as the amygdala and thalamic and pontine nuclei. The distribution and abundance of activated microglia and astrocytes correlate with Aβ deposition.	Mice develop age-associated cognitive impairment from 8 months with impaired acquisition of spatial learning in the water maze.

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PS/APP

Observed

X
Plaques at 26

Large amounts of Aβ accumulate in the cerebral cortex and hippocampus, starting around 6 months and increasing with age. Other brain regions are affected later. Both diffuse and fibrillar plaques form (Gordon et al., 2002).
X
Neuronal Loss at 79

Neuronal loss in the CA1 region of the hippocampus has been reported at 22 months accompanied by reduced glucose utilization (Sadowski et al., 2004).
X
Gliosis at 26

GFAP-positive astrocytes appear first in the cortex in the vicinity of the developing Aβ deposits. Numbers increase with age, becoming confluent. Numbers of resting microglia (positive for complement receptor-3) increase in the vicinity of deposits at 6 months, but activated microglia (positive for MHC-II) are negligible before 12 months and more variable (Gordon et al., 2002).
X
Cognitive Impairment at 12

Double and single transgenic mice had reduced spontaneous alternation performance in a “Y” maze, a test of spatial memory, at 12-14 weeks, before substantial Aβ deposition (Holcomb et al., 1998). Progressive age-related cognitive impairment is seen later in select tasks (e.g. water maze acquisition and radial arm water maze working memory)(Arendash et al., 2001).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C)	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter, cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation.	Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels.

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PS cDKO

Observed

X
Neuronal Loss at 9

Significant increase (about 8-fold) in apoptotic neurons at 2 months of age, although the total number of cortical neurons is not significantly altered due to the low basal level of apoptosis in the cerebral cortex. By 4 months of age, the cumulative loss of cortical neurons reaches about 9 percent of all cortical neurons.
X
Gliosis at 17

Astrogliosis and microgliosis; up-regulation of GFAP and other inflammatory markers are observed in the neocortex and hippocampus at 6 months, and this increases with age (Wines-Samuelson et al., 2010, Beglopoulos et al., 2004).
X
Synaptic Loss at 26

Reduction in synaptophysin immunoreactivity in hippocampal CA1 pyramidal neurons by 6 months. Reduction in dendritic spines by 9 months (Saura et al., 2004).
X
Cognitive Impairment at 9

Deficits in the Morris water maze and contextual fear conditioning are mild at 2 months, but become more severe with age (Saura et al., 2004).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
PSEN1, PSEN2		PSEN1: Conditional Knock-out; PSEN2: Knock-Out	Alzheimer's Disease	At 2 months the number of apoptotic neurons is elevated about 8-fold. By 6 months, about 18 percent of of cortical neurons are lost. Up-regulation of inflammatory markers and progressive astrogliosis and microgliosis in the neocortex and hippocampus.	Impairments in hippocampal learning and memory as indicated by Morris water maze and contextual fear conditioning evident by 2 months and worsens with age.

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Psen1 L435F knock-in

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Psen1, App	PSEN1 L435F	Psen1: Knock-In; App: Knock-In	Alzheimer's Disease	None observed in 15-day-old rats.	Unknown.

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PWK.APP/PS1

Observed

X
Plaques at 32

Thioflavin S-positive amyloid plaques are present in the cortex and CA1 region of the hippocampus by 8 months of age, with females having more plaques in the cortex than males.
X
Gliosis at 33

Plaque-associated microgliosis observed by 8 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques and plaque-associated gliosis by 8 months.	Transgenic mice are hyperactive and aggressive. Working memory and short-term memory are intact at 7 to 8 months, as assessed by tests in the Y-maze.

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rTg9191

Observed

X
Plaques at 35

Plaques emerge first in the cerebral cortex, starting around 8 months of age. This is followed by plaques in the hippocampus at 10.5 to 12.5 months of age. Some dense core plaques develop.
X
Neuronal Loss at 9

Expression of the tetracycline transactivator (tTA) resulted in reduced forebrain weight and smaller dentate gyri in rTg9191 mice compared to non-Tg littermates. This effect was also observed in mice expressing tTA alone, and is thought to be a developmental effect, as it was observed even in young mice (e.g., 2-6 months of age).
X
Gliosis at 104

rTg9191 mice develop reactive gliosis (astrocytosis and microgliosis) in the vicinity of dense-core plaques by 24 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP V717I (London)	APP: Transgenic	Alzheimer's Disease	Age-associated pathology in the cerebral cortex and hippocampus starting at 8 and 10½-12½ months of age, respectively. Gliosis and hyperphosphorylated tau in the vicinity of dense-core plaques. Fibrillar oligomeric species, e.g., Aβ dimers.	No transgene-related deficits seen in Morris water maze (4, 12, 21, 24, months of age) or fixed consecutive-number (23 months of age) tests.

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rTgTauEC

Observed

X
Tangles at 78

By 18 months of age, Gallyas silver-positive staining is observed, indicative of paired helical filaments. This is followed by thioflavin-S staining at 24 months. Tau pathology develops first in neurons of the medial EC expressing human tau, followed by neurons in the dentate gyrus, CA1 and CA2/3(de Calignon et al., 2012).
X
Neuronal Loss at 83

Neuronal loss is detectable by 24 months of age in areas with transgene expression (e.g. layer II of the EC and parasubiculum), compared with age-matched mice expressing only tTA. Significant neuronal loss was not observed at 21 months (de Calignon et al., 2012).
X
Gliosis at 104

Microglial activation and astrogliosis by 24 months of age, in conjunction with axonal degeneration and neuronal loss (de Calignon et al., 2012).
X
Synaptic Loss at 104

By 24 months of age pre- and post-synaptic densities were reduced in the middle third of the molecular layer of the dentate gyrus as measured by synapsin-1 and PSD-95 staining (de Calignon et al., 2012).
X
Changes in LTP/LTD at 70

At 16 months of age, subtle differences in electrophysiological properties have been observed in the perforant pathway, including a decrease in LTP and an increase in the probability of neurotransmitter release (Polydoro et al., 2014).
X
Cognitive Impairment at 70

Very mild and specific deficits in contextual fear conditioning at 16 months of age, but no deficits in the radial arm maze (Polydoro et al., 2014).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT P301L	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss.	Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test.

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rTg(tauP301L)4510

Observed

X
Tangles at 17

Pretangles as early as 2.5 months. Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months.
X
Neuronal Loss at 24

Decreased (~60%) CA1 hippocampal neurons by 5.5 months with significant loss in brain weight. Progressive loss of neurons and brain weight in 7 and 8.5 month mice with ~23% of CA1 pyramidal cells remaining at 8.5 months. Gross atrophy of the forebrain by 10 months.
X
Synaptic Loss at 35

Significant loss of dendritic spines at 8-9 months (~30% decrease in spine density in somatosensory cortex).
X
Cognitive Impairment at 11

Retention of spatial memory (Morris Water Maze) became impaired from 2.5 to 4 months. No significant motor impairments up to 6 months. Spatial memory improved when transgene suppressed by dox.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT P301L	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60 percent) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (six to eight week) suppression of transgenic tau.	Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved.

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SHR24

Observed

X
Tangles at 38

Argyrophilic neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem.
X
Synaptic Loss at 60

Decreased levels of synaptophysin and a decreased number of synaptic vesicles per synapse in animals at the end of the lifespan of this line.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT		MAPT: Transgenic	Alzheimer's Disease	Neurofibrillary tangles accumulate in cortex, hippocampus, thalamus, and brainstem, beginning at 9 to 10 months. No neuron loss was observed in the hippocampus or cortex.	SHR24 rats exhibit age-dependent impairments in several neurobehavioral tests; hind-limb clasping during the tail-hang test is one of the earliest abnormalities to appear, evident by 3.5 months of age.

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SHR318

Observed

X
Tangles at 38

Argyrophilic neurofibrillary tangles are particularly prominent in the brainstem and spinal cord.
X
Cognitive Impairment at 18

At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT		MAPT: Transgenic	Alzheimer's Disease	Neurofibrillary tangles first appear at 9 months and are particularly prominent in the brainstem and spinal cord. Axonal degeneration is observed in the brainstem and spinal cord of 10- to 12-month animals.	At 4.5 months, rats show normal learning, but deficits in spatial memory, in the Morris water maze. Reflexes and sensorimotor coordination are impaired at 7 months.

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SHR72

Observed

X
Tangles at 30

Neurofibrillary tangles, demonstrated by Gallyas silver stain, are present in the brainstem and spinal cord.
X
Gliosis at 29

Astrogliosis and microgliosis are present in brainstem regions bearing neurofibrillary tangles.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT		MAPT: Transgenic	Alzheimer's Disease	Neurofibrillary tangles, demonstrated by Gallyas silver stain, were found the brainstems and spinal cords of terminal stage (7- to 8-month old) animals. Chromatolytic neurons and damaged axons were also observed at this stage.	Sensorimotor deficits and loss of muscle strength are apparent at 3 months. This stage lasted about three months, and then rats experienced a rapid, dramatic decline in neurological function, succumbing within several days.

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SHRSP/FAD

Observed

X
Plaques at 69

Diffuse amyloid plaques observed at 16-18 months, the only age examined to date.
X
Tangles at 70

Occasional neurons appear to contain globose neurofibrillary tangles, as revealed by immunostaining using an antibody directed against tau phosphorylated at serine 422, an epitope found in paired helical filaments.
X
Gliosis at 71

Hypertrophied microglia and elevated levels of GFAP observed at 16-18 months, the only age examined to date.
X
Cognitive Impairment at 72

Working memory deficits as assessed by novel object recognition, but not as assessed by spontaneous alternation in the Y-maze, at 16-18 months, the only age examined to date.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease, Vascular Dementia	Amyloid plaques, microgliosis, and possible astrogliosis. Occasional neurons appear to contain paired helical filament tau. Demyelination. Reduced calbindin immunoreactivity and increased levels of caspase-cleaved actin may indicate neuron loss.	Hyperactive. Working memory deficits as assessed by novel object recognition, but not as assessed by spontaneous alternation in the Y-maze.

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Snx1D465N/APOE4/Trem2R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Snx1, APOE, Trem2	TREM2 R47H	Snx1: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Sorl1*A528T

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Sorl1	SORL1 A528T (SNP 13)	Sorl1: Knock-In	Alzheimer's Disease

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Sorl1A528T/APOE4/Trem2R47H

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Sorl1, APOE, Trem2	TREM2 R47H, SORL1 A528T (SNP 13), APOE C130R (ApoE4)	Sorl1: Knock-In; APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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SORL1 transgenic (Cre-inducible)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
SORL1		SORL1: Transgenic	Alzheimer's Disease	Unknown.	Normal performance in the Morris Water Maze.

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SORLA-deficient

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Sorl1		Sorl1: Knock-Out	Alzheimer's Disease	Mice do not generate amyloid plaques. Disrupted nigrostriatal connectivity and thinner inner nuclear layer of the retina.	Hyperactivity and reduced anxiety, compared with wild-type mice.

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TAS10 (thy1-APPswe)

Observed

X
Plaques at 52

Fibrillar amyloid plaques develop by 12 months in the cortex and hippocampus.
X
Gliosis at 26

Astrogliosis and microgliosis underway by 6 months of age in the dentate gyrus.
X
Synaptic Loss at 104

TAS10 mice initially have more synapses than non-Tg mice; specifically, greater numbers of synapses per neuron were documented at 12 and 18 months of age. However, by 24 months of age, TAS10 mice have fewer synapses than non-Tg mice.
X
Cognitive Impairment at 26

Deficits in spatial learning present by 6 months of age as measured by the Morris water maze. No difference from non-Tg at 2 months of age. Deficits in Y maze at 12 months. No deficit in fear conditioning up to 24 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish)	APP: Transgenic	Alzheimer's Disease	Age-related accumulation of Aβ in the hippocampus and cortex leading to plaque deposition by 12 months of age. Early gliosis and dystrophic neurites, not limited to the vicinity around plaques. Changes in synaptic morphology and number, along with increased number of lysosomes.	Deficits in spatial memory prior to Aβ deposition, including deficits in the Morris water maze by 6 months Deficits in spontaneous alternation behavior in the Y maze by 12 months. No deficit in fear conditioning.

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TASTPM (TAS10 x TPM)

Observed

X
Plaques at 26

Aβ begins to deposit at 3 months of age, with fibrillar plaques evident by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid is also observed. Plaque pathology is more severe in female mice.
X
Gliosis at 28

Greater numbers of reactive astrocytes and microglia by 6 months of age in the hippocampus and cortex, predominantly near amyloid plaques.
X
Cognitive Impairment at 26

Age-dependent impairment in object recognition memory starting around 6 months of age for both sexes. No impairment at 3 to 4 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 M146V	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Aβ deposits beginning at 3 months of age, with fibrillar plaques by 6 months in the cerebral cortex and hippocampus. Some vascular amyloid. Plaques surrounded by dystrophic neurites and reactive glia. No tangles or neuronal loss. Female mice have more rapid and severe amyloid pathology.	Age-dependent impairment in object recognition memory starting around 6 months of age.

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Tau35

Observed

X
Tangles at 35

Abnormally phosphorylated tau detected at two months and by eight months tau was mislocalized and misfolded and dystrophic neurites were observed. Tangle-like structures observed in the hippocampus by 14 months.
X
Synaptic Loss at 61

At 14 months synapsin1 protein levels were decreased but synaptophysin levels remained at wild-type levels.
X
Cognitive Impairment at 36

In the Morris water maze, Tau35 had the same performance as wild-type animals at six months but developed progressive deficits by eight months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT		MAPT: Transgenic	Progressive Supranuclear Palsy, Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Progressive tau pathology in the hippocampus, including abnormally phosphorylated and misfolded tau, mislocalized tau, and tangle-like structures. Dystrophic neurites.	Impaired spatial learning and memory in the Morris water maze. Early motor impairments, including abnormal limb clasping, Rotarod deficits and decreased grip strength.

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Tau4RTg2652

Observed

X
Cognitive Impairment at 13

Deficits in spatial learning and memory as indicated by performance in the Barnes maze at multiple time points (3, 6, 11 months of age).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT		MAPT: Transgenic	Frontotemporal Dementia, Other Tauopathy, Alzheimer's Disease	Extensive pretangle pathology throughout the brain (e.g. phospho- tau) but no mature neurofibrillary tangles and only mild oligomeric tau, restricted to the CA1 region of the hippocampus. Dystrophic neurites and axonal pathology (spheroids). No overt neuronal loss.	Motor deficits develop with age, including decreased grip strength and impaired Rotarod performance. Cognitive deficits, indicative of impaired spatial learning and memory, as assessed by the Barnes maze.

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Tau609 (Tau 10 + 16)

Observed

X
Tangles at 65

Gallyas silver-positive intracellular inclusions of hyperphosphorylated tau aggregates in the entorhinal cortex at 15 months, and in the hippocampus and cerebral cortex at 24 months, but not at 18 months.
X
Neuronal Loss at 65

Significant loss of NeuN-positive neurons in layer II of the entorhinal cortex at 15 months, and in the hippocampal CA1 region at 24 months, compared with non-Tg controls. No difference in the hippocampus at 18 months.
X
Gliosis at 52

At 12 months of age, Iba1-positive cells are observed. GFAP is observed at 24 months of age.
X
Synaptic Loss at 28

Reduced synaptic density at 6 months of age in select hippocampal areas compared to non-Tg mice and those expressing wild-type human tau. Densities in other areas were comparable until later ages (i.e., 24 months).
X
Changes in LTP/LTD at 26

Some changes in basal synaptic transmission and significant impairment of LTP evident by 6 months of age in some regions of the hippocampus.
X
Cognitive Impairment at 26

Deficits in spatial reference memory by 6 months of age as measured by the Morris water maze. No difference from non-Tg littermates at 4 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT IVS10+16 C>T	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease, Other Tauopathy	Aggregated tau in neurons of the entorhinal cortex, hippocampus, and cerebral cortex at advanced ages. Intraneuronal accumulation of tau oligomers in the hippocampus. Neuronal loss in the entorhinal cortex and hippocampus. Gliosis. Some hippocampal areas affected by age-related synaptic dysfunction and reduced synaptic density.	Impaired spatial reference memory as measured by the Morris water maze by 6 months of age.

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TauA152T-AAV

Observed

X
Neuronal Loss at 10

Neuron loss in cortex, seen at 3 months.
X
Gliosis at 11

Astrogliosis, but not microgliosis, seen at 3 months.
X
Cognitive Impairment at 12

Deficits in contextual and cued fear conditioning, seen at 3 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT A152T	MAPT: Virus	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Neuron loss and astrogliosis were observed in the cortices of 3-month-old mice.	Compared with GFP-AAV controls, Tau^A152T-AAV mice showed deficits in contextual and cued fear conditioning, increased hyperactivity, and decreased rearing in the open-field test, and spent more time in the open arms of the elevated plus maze. Tau^A152T-AAV mice also exhibited motor impairment on the Rotarod.

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TauC3 (Transgenic caspase-cleaved tau)

Observed

X
Synaptic Loss at 6

Reduced levels of synaptic proteins as early as 1.3 months, including synaptophysin. Further reductions in 3 and 6-month-old animals.
X
Cognitive Impairment at 6

Learning and memory impairments as early as 1.3 months in several behavioral tests including the Y-maze, passive avoidance, and novel object recognition.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT		MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	No significant cell loss or astrogliosis in the brain. Age-dependent reduction in synaptic proteins (e.g. synaptophysin, PSD95) by 1.3 to 3 months of age. Hyperphosphorylated tau oligomers and aggregates.	Learning and memory deficits by 1.3 to 3 months of age, as assessed by the Y-maze and passive avoidance tests. No significant motor impairment.

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TauΔK280 ("Proaggregation mutant")

Observed

X
Tangles at 104

Mature tangles are observed only at advanced age (>24 months), but extensive pre-tangle pathology develops with as little as three months of transgene expression. This includes mislocalization of tau to the somatodendritic compartment, conformational changes indicative of aggregation, and hyperphosphorylation (e.g. Ser 262, Ser 356).
X
Synaptic Loss at 57

Electron microscopy showed a moderate decrease in spine synapses in the CA1 region of the hippocampus following 13 months of gene expression.
X
Changes in LTP/LTD at 52

Impaired hippocampal LTP in the CA1 and CA3 areas.
X
Cognitive Impairment at 70

Cognitive deficits in the Morris water maze and in passive-avoidance paradigms.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT K281del (K280del)	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Abundant pre-tangle pathology, but only rare mature tangles, and only at advanced ages. Tau pathology included mislocalization of tau to the somatodendritic compartment, aggregation, and hyperphosphorylation.	Unknown.

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Tau P301L

Observed

X
Tangles at 35

Hyperphosphorylation, conformational changes, and aggregation of tau resulting in tangle-like pathology by 8 months.
X
Gliosis at 30

Astrogliosis by 7 months.
X
Changes in LTP/LTD at 26

Deficit in LTP in CA1 region of the hippocampus at 6 months, but enhanced LTP in the dentate gyrus at a young age (8-10 weeks).
X
Cognitive Impairment at 22

Age-associated deficit in two cognitive tests that do not depend heavily on motor ability, the passive avoidance task (significant deficit starting at 5 months, but not 2 or 3 months of age) and a novel object recognition task (significant deficit at 9 months, but not at 2, 3, 5, or 7 months of age) (Maurin et al., 2014).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT P301L	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF.	Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months.

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TauP301L-AAV

Observed

X
Tangles at 24

Argyrophilic, Thioflavin S-positive neurofibrillary tangles in cortex and hippocampus.
X
Gliosis at 12

Astrogliosis and microgliosis observed at 3 months.
X
Cognitive Impairment at 24

Deficits in cued and contextual fear conditioning observed at 6 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT P301L	MAPT: Virus	Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy	Neurofibrillary tangles and gliosis, but no cortical neuron loss, at 6 months of age.	Hyperactivity in the open field, decreased time spent in the center of open field, more time spent in the open arms of the elevated plus maze, and deficits in cued and contextual fear conditioning at 6 months of age.

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Tau P301S (Line PS19)

Observed

X
Tangles at 23

Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem and spinal cord at six months with progressive accumulation (Yoshiyama et al., 2007).
X
Neuronal Loss at 39

Neuron loss in the hippocampus and entorhinal cortex by nine to12 months, as well as in the amygdala and neocortex becoming more severe by 12 months (Yoshiyama et al., 2007).
X
Gliosis at 11

Microgliosis at three months, especially in the white matter of the brain and spinal cord. Increased microgliosis by six months in white and gray matter of the hippocampus, amygdala, entorhinal cortex, and spinal cord. Microglial activation precedes astrogliosis (Yoshiyama et al., 2007).
X
Synaptic Loss at 13

Synaptophysin immunoreactivity decreased progressively from three to six months in the CA3 region of the hippocamus. Impaired synaptic function (Yoshiyama et al., 2007).
X
Changes in LTP/LTD at 26

Reduced LTP in the CA1 region of the hippocampus at six months. Altered basal synaptic transmission (smaller fiber volley amplitude, fEPSP slopes, and amplitudes) (Yoshiyama et al., 2007). Impaired hippocampal LTP as measured in freely moving mice (Lasagna-Reeves, 2016).
X
Cognitive Impairment at 27

Impairments in spatial learning and memory ability in the Morris water maze in six-month-old animals (Takeuchi et al., 2011). Impaired memory in assays of contextual fear conditioning (Lasagna-Reeves 2016).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT P301S	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis.	Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months.

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TauPS2APP

Observed

X
Plaques at 17

Rare amyloid plaques at 4 months, plaques become more abundant with age. By 8 months the number of amyloid plaques increases considerably in the subiculum and the CA1 region of the hippocampus (Grueninger et al., 2010).
X
Tangles at 70

Abnormally phosphorylated tau is detectable at 4 months in both TauPS2APP and tau single transgenic mice especially in the subiculum, amygdala, and the CA1 region of the hippocampus. Tau pathology increases with age with numerous tangle-like deposits in the hippocampus confirmed by Gallyas silver staining at 16 months (Grueninger et al., 2010).
X
Cognitive Impairment at 17

Impairment is not age-associated and does not progress from age 4 months to 12 months (Grueninger et al., 2010).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, MAPT, PSEN2	APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I (Volga)	APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic	Alzheimer's Disease	Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss.	Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology.

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Tau R406W transgenic

Observed

X
Tangles at 78

Congophilic tau inclusions in a subset of forebrain neurons around 18 months of age. Detected by Congo red, thioflavin S, and Gallyas silver stain.
X
Cognitive Impairment at 70

Impairments in the contextual and cued fear conditioning test at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT R406W	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments.	Impairments in contextual and cued fear conditioning at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits.

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TauRDΔK280 (“Proaggregation mutant”)

Observed

X
Tangles at 9

Tau tangles and aggregates with as little as 2-3 months of transgene expression. Tangles start in the entorhinal cortex and amygdala and spread to the neocortex by 15 months. Heterogeneous tangle morphology, including flame-shaped.
X
Neuronal Loss at 22

Neuronal loss in the dentate gyrus (granule neurons) following 5 months of transgene expression. Shrinkage of the molecular layer of the hippocampus.
X
Gliosis at 91

Astrogliosis in the hilus region of the hippocampus after 21 months of transgene expression. Additional increases in GFAP-positive astrocytes in the entorhinal and piriform cortices.
X
Synaptic Loss at 41

Hippocampal synaptic loss as indicated by multiple measures following 9.5 months of transgene expression. Reduced synaptophysin immunoreactivity and reduced number of spine synapses as measured by electron microscopy.
X
Changes in LTP/LTD at 43

Multiple deficits in synaptic plasticity, including deficits in LTP and LTD, after 10 months of transgene expression. Functional changes are associated with structural synaptic changes, local calcium dysregulation, and a decrease in the synaptic vesicle pool.
X
Cognitive Impairment at 43

Learning and memory impairments are apparent after 10 months of transgene expression as assessed by the Morris water maze and passive avoidance tasks.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT K281del (K280del)	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	Tau aggregates and tangles as early as 2-3 months after gene expression. Gallyas silver-positive neurons abundant in the entorhinal cortex and amygdala, spreading to the neocortex by 15 months. “Ballooned” neurons. Astrogliosis. Synaptic structural changes and reduced synaptic number. Hippocampal neuronal loss.	Reversible learning and memory deficits in the Morris water maze and passive avoidance test. No significant motor deficit, although slight reduction in Rotarod performance.

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Tau V337M

Observed

X
Tangles at 48

Fibrillar staining in the hippocampus of 11 month old animals by Congo red birefringence. Absent in 4 month old mice, indicating the formation of these neurofilament-like structures occurs between 4 and 11 months (Tanemura et al., 2001).
X
Neuronal Loss at 43

Evidence of hippocampal neuronal degeneration in 10 month old animals: irregularly shaped neurons with tau pathology that stained with propidium iodide. As characteristics of apoptosis were not observed, the neurons were thought to be undergoing non-apoptotic atrophic degeneration (Tanemura et al., 2002).
X
Changes in LTP/LTD at 65

In hippocampal slices there was an attenuation of the amplitude of Schaffer collateral evoked hippocampal depolarization (Tanemura et al., 2002).
X
Cognitive Impairment at 48

Behavioral abnormalities measured in 11 month-old mice. They spent more time in the open arms of the elevated plus maze and had greater overall locomoter activity. No differences in the Morris water maze compared with non-transgenic mice, suggesting the transgenic animals retain spatial recognition abilities (Tanemura et al., 2002).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT V337M	MAPT: Transgenic	Alzheimer's Disease, Frontotemporal Dementia	SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure.	Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze.

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TBA42

Observed

X
Plaques at 52

Very rare extracellular Aβ deposits.
X
Neuronal Loss at 52

Age-dependent neuronal loss in the CA1 region of the hippocampus. No difference from wild-type mice at 3 and 6 months of age, but approximately 35% loss at 12 months of age.
X
Gliosis at 52

Marked gliosis in the hippocampus as measured by GFAP staining at 12 months.
X
Cognitive Impairment at 54

Age-dependent deficits in working and spatial reference memory at 12 months, but not at 3 and 6 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP		APP: Transgenic	Alzheimer's Disease	Intraneuronal accumulation of Aβ peptides in the hippocampus by 3 months and in cerebellar nuclei by 6 months. Marked gliosis in the hippocampus by 12 months. Very rare extracellular Aβ deposits.	Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at 3 or 6 months. Early and persistent decrease in anxiety in the elevated plus maze. Comparable to wild-type in general motor coordination at 3 and 6 months as indicated by the balance-beam test, but impairment at 12 months.

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TcMAC21

Observed

X
Changes in LTP/LTD at 14

Reduction in LTP compared to controls.
X
Cognitive Impairment at 13

Behavioral (Morris water maze and open field) and physiological results showed significant deficits in learning, memory, and synaptic plasticity. No alteration in nesting abilities.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
		Multi-transgene	Down's Syndrome, Alzheimer's Disease	Elevated APP, Aβ40, and Aβ42 in brain at 15–24 months, but no amyloid plaque pathology. Enlarged lateral ventricles and superior colliculus, and smaller cerebellum.	Learning and memory deficits.

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Tg12099 rat

Observed

X
Tangles at 26

Neurofibrillary tangles visualized by Bielschowsky silver staining were present in the piriform and entorhinal cortices of terminal Tg12099 rats homozygous for the transgene. Tangles also stained with ThioflavinS. Tangles were absent in hemizygous rats.
X
Neuronal Loss at 39

Pronounced neurodegeneration in the forebrains of Tg12099 homozygotes at terminal stages. Neuronal loss and concordant atrophy of piriform/entorhinal cortices were first observed between 9 and 12 months and continued to worsen with age.
X
Gliosis at 27

Increased GFAP immunoreactivity in the brains of terminal Tg12099 homozygotes compared with aged hemizygotes. Astrogliosis matches the spatiotemporal pattern of tau deposition, becoming apparent in the amygdala and entorhinal cortex as early as 6 to 7 months of age.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT P301S	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	Tau pathology, including neurofibrillary tangles, forebrain neurodegeneration, and astrogliosis in homozygotes. Hemizygotes exhibit little pathology, save for a few AT8-immunoreactive neurons in the entorhinal cortices of aged animals.	Ataxia, bradykinesia, and seizures reported in aging homozygotes.

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Tg2576

Observed

X
Plaques at 48

Numerous parenchymal Aβ plaques by 11-13 months.
X
Gliosis at 43

Increase in microglial density and size in plaque-forming areas of the brain including the hippocampus, frontal cortex, entorhinal cortex, and occipital cortex in 10-16 month old hemizygotes (Frautschy et al., 1998).
X
Synaptic Loss at 20

Dendritic spine loss by 4.5 months In the CA1 region of the hippocampus (Lanz et al., 2003).
X
Changes in LTP/LTD at 22

By 5 months, there was a decline in LTP in the dentate gyrus after perforant path stimulation compared to wild-type; impairment was not observed at 2 months (Jacobsen et al., 2006). Both the CA1 and dentate gyrus of aged mice (>15 months) are impaired (Chapman et al., 1999). Differences have been observed between the Schaffer collateral and mossy fiber pathways (Jung et al., 2011).
X
Cognitive Impairment at 26

Impaired spatial learning, working memory, and contextual fear conditioning at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish)	APP: Transgenic	Alzheimer's Disease	Numerous parenchymal Aβ plaques by 11-13 months with some vascular amyloid. Oxidative lipid damage, astrogliosis and microgliosis. No tangles or neuronal loss.	Impaired spatial learning, working memory, and contextual fear conditioning reported at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months.

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Tg2576/Tau(P301L) (APPSwe-Tau)

Observed

X
Plaques at 39

Plaques develop gradually with age. No plaques at 5 months. Very few small plaques at 6 and 7 months. By 9 months plaques scattered throughout the cortex, hippocampus and amygdala, continue to increase at 12 months. Similar distribution as Tg2576.
X
Tangles at 13

Neurofibrillary tangles in the spinal cord and pons as early as 3 months, but more consistent and numerous by 6 months. Tangles morphologically similar to those in JNPL3 mice but older bigenic female mice had a marked increase in neurofibrillary tangles in limbic areas by 6 months, especially the olfactory cortex, entorhinal cortex and amygdala (Lewis et al., 2001).
X
Gliosis at 13

Reactive astrocytes and microglia as early as 3 months in the hippocampus as measured by GFAP and CD45. Increased astrocytosis with age especially in limbic areas with the most neurofibrillary tangles. Microglia especially concentrated around plaques at 9 and 12 months (Lewis et al., 2001).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, MAPT	APP K670_M671delinsNL (Swedish), MAPT P301L	APP; MAPT: Transgenic	Alzheimer's Disease	Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis.	Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming.

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Tg4-42

Observed

X
Neuronal Loss at 35

Age- and dose-dependent neuronal loss in the hippocampus CA1 region of hemizygous and homozygous mice. Compared with wild-type, hemizygous mice had 38% neuronal loss at 8 months, and 49% loss at 12 months. No difference at 3 months.
X
Gliosis at 9

Reactive microglia and astrocytes in the hippocampus starting at 2 months.
X
Synaptic Loss at 37

Altered synaptophysin staining in the CA3 region of the hippocampus. More pronounced in homozygous mice than hemizygous mice at 8 months.
X
Cognitive Impairment at 35

Spatial reference memory is impaired as assessed by Morris water maze at 8 months in homozygous mice and 12 months in hemizygous mice. Deficit is age-dependent and is not detected at 3 months. Impaired contextual fear conditioning at 12 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP		APP: Transgenic	Alzheimer's Disease	Aβ4-42 is dectable starting at two months, predominantly in the CA1 region of the hippocampus, but also in the occipital cortex, piriform cortex, striatum, and superior colliculus. Age- and dose-dependent hippocampal neuronal loss is seen in the CA1 region as well as microgliosis and astrogliosis.	Age-dependent spatial learning deficit as demonstrated in the Morris water maze, specifically, the absence of a preference for the target quadrant starting at eight months in homozygous mice and at 12 months in hemizygous mice. Impaired contextual fear conditioning.

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tg-APPSwe

Observed

X
Plaques at 52

Plaques are detectable at approximately 12 months and are heterogeneous in morphological structure and size, as well as in terms of fluorescence emitted when stained with luminescent polymers (conformational amyloid ligands)(Philipsson et al., 2009).
X
Gliosis at 52

Microgliosis and astrogliosis are most prominent in the hippocampus, but also found locally around deposits in the cerebral cortex and in thalamus at approximately 12 months (Philipsson et al., 2009).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish)	APP: Transgenic	Alzheimer's Disease	Extracellular amyloid deposition begins at ~12 months. Intraneuronal Aβ aggregates at ~6 months. Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1.0% (at 12 months) and 2.8% (at 18 months).	Unknown.

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Tg-ArcSwe

Observed

X
Plaques at 22

Extracellular amyloid plaque deposition starts at around 5-6 months of age (Lord et al., 2006) and is most consistently present in the cerebral cortex, hippocampus, and thalamus (Lillehaug et al., 2013).
X
Gliosis at 26

Microgliosis and astrogliosis most prominent in the hippocampus, but also locally around deposits in the cerebral cortex and thalamus.
X
Cognitive Impairment at 17

Transgene-dependent spatial learning impairment in the Morris water maze (4-8 months) (Lord et al., 2009) and in an Intellicage-based Passive Avoidance test (16 months)(Codita et al., 2010).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP E693G (Arctic)	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy	Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus.	Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months.

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TgCRND8

Observed

X
Plaques at 13

Amyloid deposition progresses with age. Thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques appear first in the subiculum, amygdala and frontal cortex, spread to the dentate gyrus, the olfactory bulb, and later thalamus, cerebral vasculature, and striatum, followed by the cerebellum and brain stem (Chishti et al., 2001).
X
Neuronal Loss at 26

Variable cell loss by region. No difference in overall cell count, but fewer hippocampal neurons at 6 months (Brautigam et al., 2012).
X
Gliosis at 13

Microglia activation appears simultaneously with Aβ deposition, with only rare activated microglia at 9-10 weeks, but by 13-14 weeks microglia cluster around Aβ deposits in the cerebral cortex and hippocampus; numerous by 20 weeks. Robust astrogliosis slightly later with clusters of GFAP+ astrocytes emerging around plaques at 13-14 weeks (Dudal et al., 2004).
X
Synaptic Loss at 26

Reduced synaptophysin immunoreactivity in the vicinity of plaques at 6 months (Adalbert et al., 2009).
X
Changes in LTP/LTD at 26

In hippocampal slices from 6- to 12-month-old mice basal excitatory synaptic transmission (as assessed by I/O relationships) and LTP at CA1 are reduced in TgCRND8 mice compared with wild-type mice (Kimura et al., 2012).
X
Cognitive Impairment at 13

Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze, present by 3 months (Chishti et al., 2001).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP V717F (Indiana)	APP: Transgenic	Alzheimer's Disease	Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months .	Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests.

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TgDimer

Observed

X
Changes in LTP/LTD at 28

LTP decays more rapidly, compared with wild-type mice.
X
Cognitive Impairment at 28

Learning deficits in the Morris Water Maze.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP S679C	APP: Transgenic	Alzheimer's Disease, MCI due to AD	Intracellular Aβ immunoreactivity in the hippocampus and cortex, beginning by 12 months. No amyloid plaques, hyperphosphorylated tau, microgliosis, astrogliosis, or neuron loss through 24 months.	Learning deficits, as well as indicators of increased anxiety and depression, by 7 months.

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TgF344-AD

Observed

X
Plaques at 24

Age-dependent accumulation of amyloid plaques in hippocampus and cortex between 6 and 26 months of age.
X
Tangles at 64

Structures similar in appearance to neurofibrillary tangles revealed by Gallyas staining and immunostaining using an antibody directed against phospo-tau.
X
Neuronal Loss at 64

Approximate 40 percent loss of neurons in hippocampus and cortex by 16 months.
X
Gliosis at 23

Microgliosis and astrogliosis are apparent by 6 months.
X
Cognitive Impairment at 25

Deficits in reversal learning in the Morris water maze apparent by 6 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, microgliosis, and astrogliosis by 6 months. Neurofibrillary tangle-like structures at 16 months. Approximate 40 percent loss of neurons in hippocampus and cortex by 16 months.	Earliest reported deficits are in reversal learning in the Morris water maze, apparent by 6 months.

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Tg-SwDI (APP-Swedish,Dutch,Iowa)

Observed

X
Plaques at 13

Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Amyloid-β deposits in the subiculum, hippocampus, and cortex at ~3 months. By ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (Davis et al., 2004).
X
Gliosis at 26

Pronounced increase in the number of GFAP-positive astrocytes and activated microglia with age (6-24 months) especially in the thalamus and subiculum and to a lesser extent in the cortex (Miao et al., 2005).
X
Cognitive Impairment at 13

Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months; beginning at 3 months took longer to find the escape hole. No difference in mobility, strength or coordination (Xu et al., 2007).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP	APP K670_M671delinsNL (Swedish), APP E693Q (Dutch), APP D694N (Iowa)	APP: Transgenic	Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type	Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months.	Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination.

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THY-Tau22

Observed

X
Tangles at 13

Heterozygous animals develop tau pathology starting at 3-6 months. Pathology becomes more severe and widespread with age. Neurofibrillary tangle-like inclusions occur (Gallyas and MC1+) along with rare ghost tangles and paired helical filament-like structures (Schindowski et al., 2006).
X
Neuronal Loss at 52

Loss of cells in the CA1 region of the hippocampus from 12 months as measured by DAPI staining and Nissl/cresyl-violet (Schindowski et al., 2006). Also, a significant reduction in the number of choline acetyltransferase (ChAT)-immunopositive cholinergic neurons in the medial septum has been reported (Belarbi et al., 2011).
X
Gliosis at 13

Age-dependent increase in the number of GFAP+ astrocytes in the hippocampus (hilus, CA1, CA3), cerebral cortex, corpus callosum (Schindowski et al., 2006).
X
Changes in LTP/LTD at 39

Altered paired pulse facilitation (PPF), a form of presynaptic short-term plasticity in 9-10 month old heterozygous animals: PPF increased at 10 ms. Also at this age, impaired maintenance of long term depression as compared with wild-type littermates (Van der Jeugd et al., 2011). Deficit in basal synaptic transmission in the hippocampus, but normal LTP (Schindowski et al., 2006).
X
Cognitive Impairment at 26

Non-spatial memory affected as early as 6 months; spatial memory impaired only after 9 months (Van der Jeugd et al., 2013). Impaired appetitive responding (Lo et al., 2013).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT G272V, MAPT P301S	MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis.	Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity.

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TMHT (Thy-1 mutated human tau)

Observed

X
Tangles at 17

Tangles at 4 months and progress with age.
X
Cognitive Impairment at 22

Cognitive impairment by 5 months as measured by the Morris Water Maze.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
MAPT	MAPT V337M, MAPT R406W	MAPT: Transgenic	Alzheimer's Disease	Increased total tau, and phosphorylated tau (Thr181, Ser199, Thr231) in amygdala and hippocampus starting at 3 months.	Spatial memory deficits starting at 5 months (Morris water maze). Olfactory deficits at 5 months (Buried food test). No motor deficits (rota rod, beam walk) or depressive behavior (forced swim test).

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TREM2-BAC

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
TREM2		TREM2: Transgenic	Alzheimer's Disease	No obvious neuropathology is observed at 4, 7 and 11 months of age.	Normal contextual fear conditioning at 10 months of age.

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TREM2-BAC X 5xFAD

Observed

X
Plaques at 28

Observed at 7 months, the youngest age examined.
X
Gliosis at 28

Microgliosis observed; however, fewer plaque-associated microglia and altered microglial morphology (more ramified processes) compared with 5xFAD at 7 months, the only age examined.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
TREM2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques with plaque-associated microgliosis. Reduced plaque burden, altered microglial and plaque morphology, and less severe plaque-associated neuritic dystrophy, compared with 5xFAD.	5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired.

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Trem2-H157Y knock-in

Observed

X
Changes in LTP/LTD at 24

Enhanced paired-pulse facilitation and long-term potentiation at Schaffer collateral-CA1 synapses in 6-month-old mice homozygous for the H157Y Trem2 allele.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2	TREM2 H157Y	Trem2: Knock-In	Alzheimer's Disease	Microglial density and morphology did not differ between carriers of the H157Y variant and wild-type mice.	Trem2-H157Y knock-in did not differ from wild-type mice at 6 months of age in tests of anxiety, associative memory, and spatial working memory.

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Trem2-H157Y x 5xFAD

Observed

X
Plaques at 16

Decreased plaque burdens and densities in 5xFAD;Trem2^H157Y/H157Y compared with 5xFAD;Trem2^+/+ at 8.5 months, but genotypes similar at 4 months.
X
Gliosis at 16

Decreased microgliosis and astrogliosis in 5xFAD;Trem2^H157Y/H157Y compared with 5xFAD;Trem2^+/+ at 8.5 months, but genotypes similar at 4 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, APP, PSEN1	TREM2 H157Y, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Age-dependent effects on amyloid-β pathology and gliosis. At 4 months, plaque burdens, microgliosis, and astrogliosis were similar among genotypes. By 8.5 months, amyloid burdens, microgliosis, and astrogliosis were reduced in homozygous carriers of the H157Y variant, compared with 5xFAD mice homozygous for wild-type Trem2.	Unknown.

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TREM2, humanized (common variant)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
TREM2, Trem2		TREM2: Transgenic; Trem2: Knock-Out	Alzheimer's Disease	Unknown.	Unknown.

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TREM2, humanized (common variant) X 5XFAD

Observed

X
Plaques at 34

Plaques observed in 8.5-month-old mice, only age reported thus far.
X
Gliosis at 34

Microgliosis observed in 8.5-month-old mice, only age reported thus far.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, TREM2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques surrounded by activated microglia.	No data.

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TREM2, humanized (R47H)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
TREM2, Trem2	TREM2 R47H	TREM2: Transgenic; Trem2: Knock-Out	Alzheimer's Disease	Unknown.	Unknown.

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TREM2, humanized (R47H) X 5XFAD

Observed

X
Plaques at 34

Plaques observed in 8.5-month-old mice, the only age reported thus far.
X
Gliosis at 34

Microgliosis observed in 8.5-month-old mice, the only age reported thus far. Fewer plaque-associated microglia in mice expressing the R47H variant, compared with the common variant of human TREM2.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, TREM2, APP, PSEN1	TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant.	No data.

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TREM2-IPD

Observed

X
Gliosis at 12

At 3 months of age, TREM2-IPD mice had more Tmem119-positive microglia and a greater percentage of proliferating microglia than mice expressing wild-type Trem2.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2		Trem2: Knock-In	Alzheimer's Disease	At 3 months of age, TREM2-IPD mice had more Tmem119-positive microglia and a greater percentage of proliferating microglia than mice expressing wild-type Trem2.	Unknown.

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Trem2-IPDxAPP23xPS45

Observed

X
Plaques at 12

Greater numbers of plaques, particularly small plaques, and larger areas occupied by plaques in 3-month-old Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 animals. These genotype-dependent differences disappeared by 7 months.
X
Gliosis at 13

Increased microgliosis in the vicinity of plaques in 3-month-old Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 mice.
X
Synaptic Loss at 14

Compared with APP23xPS45 mice, 3-month-old Trem2-IPDxAPP23xPS45 mice had fewer and smaller puncta stained for the presynaptic marker Sv2a (synaptic vesicle glycoprotein 2A) in the vicinity of plaques. These genotype-dependent differences disappeared by 7 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 G384A	Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, plaque-associated neuritic dystrophies, microgliosis. Pathology exacerbated in Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 mice expressing wild-type Trem2, at an early—but not late—stage of plaque deposition.	Unknown.

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Trem2 KO (Colonna)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2		Trem2: Knock-Out	Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease	Microglial number remains constant and microglial size decreases with age in the corpus callosum of Trem2 KO mice, while microglial number increases and microglial size remains stable in wild-type mice.	No cognitive/behaviorial deficits observed.

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Trem2 KO (Colonna) x 5XFAD

Observed

X
Plaques at 16

Plaques present by 4 months, the earliest age studied.
X
Neuronal Loss at 32

Loss of cortical layer V neurons by 8 months, the earliest age studied.
X
Gliosis at 16

MIcrogliosis by 4 months, the earliest age studied.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, APP, PSEN1	APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V	Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes.	No data.

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Trem2 KO (Colonna) x PS19

Observed

X
Gliosis at 36

Microgliosis and astrogliosis by 9 months (the earliest age studied).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, MAPT	MAPT P301S	Trem2: Knock-Out; MAPT: Transgenic	Frontotemporal Dementia, Alzheimer's Disease	Microgliosis, astrogliosis, and brain atrophy in Trem2^-/-PS19 mice are greatly attenuated compared with Trem2^+/+PS19 animals.	No data.

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Trem2 KO (JAX)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2		Trem2: Knock-Out	Alzheimer's Disease, Frontotemporal Dementia, Nasu-Hakola Disease	No data..	No data.

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Trem2 KO (KOMP)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2		Trem2: Knock-Out	Nasu-Hakola Disease, Frontotemporal Dementia, Alzheimer's Disease	No data.	At six months, mice perform normally in the open-field test, elevated plus maze, three-chamber social-interaction test, and contextual and cued fear-conditioning test.

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Trem2 KO (KOMP) x APPPS1

Observed

X
Plaques at 9

Plaques are observed by 2 months.
X
Gliosis at 9

Gliosis is observed by 2 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1 L166P	Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Reduced plaque burden at early stages of plaque deposition but increased plaque burden at later stages, fewer plaque-associated myeloid cells and astrocytes, less phospho-tau in plaque-associated dystrophic neurites, compared with APPPS1.	No data.

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Trem2 KO (KOMP) x htau

Observed

X
Gliosis at 24

Microgliosis observed by 6 months, younger ages were not studied.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Mapt, MAPT, Trem2		Mapt: Knock-Out; MAPT: Transgenic; Trem2: Knock-Out	Nasu-Hakola Disease, Alzheimer's Disease, Frontotemporal Dementia	Tau phosphorylation and aggregation in the cortex are enhanced in htau mice lacking TREM2, but reactive microglia are smaller and their processes have fewer branches.	No data.

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Trem2*R47H(HSS)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2	TREM2 R47H	Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Trem2 R47H KI (Haass)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2	TREM2 R47H	Trem2: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Trem2 R47H KI (JAX)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2	TREM2 R47H	Trem2: Knock-In	Alzheimer's Disease	No neuron loss, amyloid plaques, or neurofibrillary tangles were observed in mice up to 24 months of age.	Locomotor activity, motor coordination, and working memory similar to wild-type at 2 and 12 months of age.

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Trem2 R47H KI (Lamb/Landreth)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2	TREM2 R47H	Trem2: Knock-In	Alzheimer's Disease	No 6E10- or Thioflavin S-positive amyloid plaques were observed at 4 months of age.	Unknown.

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Trem2 R47H KI (Lamb/Landreth) X APPPS1-21

Observed

X
Plaques at 16

Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, compared with APPPS1-21 mice homozygous for wild-type Trem2.
X
Gliosis at 16

Fewer plaque-associated myeloid cells in APPPS1-21;Trem2^+/R47H, compared with APPPS1-21 mice homozygous for wild-type Trem2.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, APP, PSEN1	TREM2 R47H, APP K670_M671delinsNL (Swedish), PSEN1 L166P	Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, fewer plaque-associated myeloid cells, and worse plaque-associated neuritic dystrophy, compared with APPPS1-21 mice homozygous for wild-type Trem2.	Unknown.

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Trem2 R47H KI x APOE4 (LOAD1)

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APOE, Trem2	TREM2 R47H, APOE C130R (ApoE4)	APOE: Knock-In; Trem2: Knock-In	Alzheimer's Disease	No neuron loss, amyloid plaques, neurofibrillary tangles, vascular leakage, myelin loss, or reactive microglia in mice up to 24 months of age.	Age-related changes in locomotor activity, motor coordination, and working memory, but no genotype-dependent differences through 24 months of age, compared with wild-type mice.

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Trem2 R47H knock-in

Observed

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2, App	TREM2 R47H	Trem2: Knock-In; App: Knock-In	Alzheimer's Disease	Unknown.	Unknown.

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Trem2*R47H(NSS)

Observed

X
Synaptic Loss at 50

Synapse loss, assessed by co-localization of the pre-synaptic marker bassoon and postsynaptic marker PSD95, by 12 months.
X
Changes in LTP/LTD at 52

Impaired basal synaptic transmission and LTP, by 12 months.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
Trem2	TREM2 R47H	Trem2: Knock-In	Alzheimer's Disease	Changes in microglial morphology at 4 months but not 12 months, compared with wild-type.	Unknown.

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Ts65Dn

Observed

X
Neuronal Loss at 26

By 6 months, there is a loss of basal forebrain cholinergic neurons in the medial septal nucleus. From 10-11 months, a decrease in ChAT+ motor neurons are observed. Additional deficits include reduced brain volume, impaired neurogenesis, decreased neuronal density, and abnormal dendritic spine morphology, which are present in earlier stages of development.
X
Gliosis at 42

Ts65Dn mice show a developmental shift from neuronal to astrocytic lineage, leading to an increased percentage of astroglial cells in the cortex and hippocampus. By 10 to 18 months, an elevated density of CD45+ microglia cells are found in the hippocampus and basal forebrain, with IBA1 upregulation at 12 months and reduced expression of the homeostatic microglial marker P2RY12 at 15 months.
X
Synaptic Loss at 65

Ts65Dn mice have more inhibitory synapses, and fewer excitatory synapses. Synaptic density is decreased in both the hippocampus and neocortex, accompanied by enlarged pre-synaptic boutons and spines. Changes in the physical distribution of afferent inputs also occur.
X
Changes in LTP/LTD at 26

Ts65Dn mice demonstrate impaired hippocampal long-term potentiation (LTP) due to excessive GABA-mediated inhibition.
X
Cognitive Impairment at 13

Ts65Dn mice exhibit reduced attention, and deficits in hippocampal-dependent functions, including contextual fear conditioning, working memory, and long-term spatial memory.

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
		Multi-transgene	Down's Syndrome, Alzheimer's Disease	Elevation of APP and soluble Aβ in the brain without Aβ plaque pathology. Changes to tau 3R/4R splicing, augmenting tau mRNA stability and tau phosphorylation. Basal forebrain neurodegeneration; loss of NE neurons in locus coeruleus; hippocampal abnormalities; cholinergic neuron loss; reduced number of proliferating cells. Neuroinflammation and oxidative stress markers.	Spatial learning and memory deficits, developmental delay in sensorimotor milestones, locomotor hyperactivity, lack of behavioral inhibition, and stereotypic behavior. Delayed motor acquisition, impaired coordination, reduced attention.

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WSB.APP/PS1

Observed

X
Plaques at 32

Thioflavin S-positive amyloid plaques are present in the cortex and CA1 region of the hippocampus by 8 months of age, with females having more plaques in the cortex than males.
X
Neuronal Loss at 34

Compared with their non-transgenic littermates, female WSB.APP/PS1 mice have fewer neurons in the cortex and in CA1. Neuron numbers in male mice do not differ between the genotypes.
X
Gliosis at 33

Plaque-associated microgliosis observed by 8 months.
X
Cognitive Impairment at 31

Deficits in short-term memory by 8 months in females (data from males unavailable).

Absent

No Data

Genes	Mutations	Modification	Disease	Neuropathology	Behavior/Cognition
APP, PSEN1	APP K670_M671delinsNL (Swedish), PSEN1: deltaE9	APP: Transgenic; PSEN1: Transgenic	Alzheimer's Disease	Amyloid plaques, plaque-associated gliosis, cerebral amyloid angiopathy; possible neuron loss in cortex and hippocampal area CA1 in females.	Transgenic mice are hyperactive. Working memory (spontaneous alternation in the Y-maze) is normal at 7 to 8 months, but short-term memory (tested in the Y-maze) is impaired in females (data from males is not available, as wild-type males are unable to perform this test).

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177 Visualizations

Phenotypes Examined

Observed

Plaques at 26

Tangles at 52

Gliosis at 30

Changes in LTP/LTD at 26

Cognitive Impairment at 17

Absent

No Data

Neuronal Loss at

Observed

Plaques at 8

Neuronal Loss at 23

Gliosis at 9

Synaptic Loss at 16

Changes in LTP/LTD at 25

Cognitive Impairment at 18

Absent

Tangles at

No Data

Observed

Plaques at 8

Neuronal Loss at 52

Gliosis at 8

Synaptic Loss at 24

Changes in LTP/LTD at 8

Cognitive Impairment at 24

Absent

No Data

Tangles at

Observed

Plaques at 39

Absent

No Data

Tangles at

Neuronal Loss at

Gliosis at

Synaptic Loss at

Changes in LTP/LTD at

Cognitive Impairment at

Observed

Plaques at 128

Changes in LTP/LTD at 40

Cognitive Impairment at 40

Absent

Gliosis at

No Data

Tangles at

Neuronal Loss at

Synaptic Loss at

Observed

Plaques at 28

Gliosis at 28

Changes in LTP/LTD at 24

Cognitive Impairment at 24

Absent

No Data

Tangles at

Neuronal Loss at

Synaptic Loss at

Observed

Synaptic Loss at 28

Changes in LTP/LTD at 29

Cognitive Impairment at 30

Absent

No Data

Plaques at

Tangles at

Neuronal Loss at

Gliosis at

Observed

Absent

No Data

Plaques at

Tangles at

Neuronal Loss at

Gliosis at

Synaptic Loss at

Changes in LTP/LTD at