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67 Models


Name	Other Names	Strain Name	Genetic Background	Gene	Mutation	Modification Info	Modification	Disease	Neuropathology	Behavior/Cognition	Other Phenotype	Availability	Primary Paper	Visualization
3xTg	3xTg-AD, The LaFerla mouse	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)	5XFAD, APP/PS1, Tg6799, Tg-5xFAD	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)	5XFAD, APP/PS1, Tg6799, Tg-5xFAD	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.		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
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
AD-BXD	5xFAD BxD	(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
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	APP(SL)PS1KI, APPxPS1-Ki, APPSL/PS1KI, APP(SL)/PS1(KI), APP/PS1KI		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 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
AppNL-G-F/MAPT double knock-in	App^NL-G-F/MAPT double knock-in, App^NL-G-F/MAPT dKI		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	APPPS1-21, APP/PS1	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	APPswe/PSEN1dE9/MAPT, APPswe/PSEN1dE9/CaMKIIa-tTa/TRE-Tg21221		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
APPsw/0; Pdgfrβ+/-	Tg2576;Pdgfrβ^+/-		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	APPSwDI/NOS2 bigenic mice, APPSDI/NOS2KO, CVN	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/PSEN1(A246E)	APPSwe (line C3-3)/PSEN1(A246E)(line N-5), APP/PS1, APPswe + PS1 (A246E), APP + PS1, AP mouse, C3-3/N-5	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)	APPSwe(line C3-3) X PS1dE9 (line S-9), C3-3/PS1-dE9, C3-3 x S-9	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)	APP/PS1, C57BL/6J APPswePsen1de9, B6.APB^Tg	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)	APP/PS1, APPswe/PS1deltaE9, line 85, APP(swe) + PSEN1DeltaE9, APPdE9, Borchelt mice	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
APP(V717I) x PS1(A246E)	APPxPS1, APP(V717I)x PS1(A246E), APP[V717I]x PS1[A246E], APP.V717I x PS1.A246E	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 reMYND offers research services with this line.	Dewachter et al., 2000	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	Willuweit et al., 2009	Yes
BACE1 cKO (Hu, Yan) X 5xFAD	BACE1^{fl/fl/UbcCreER} X 5xFAD		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
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	APOE4/Trem2*R47H/Ceacam1 knock-out	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
E2FAD	APOE2-FAD, APOE2 Targeted Replacement x 5xFAD		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	APOE3-FAD, APOE3 Targeted Replacement x 5xFAD		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	APOE4-FAD, APOE4 Targeted Replacement x 5xFAD		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	APOE4 (line1)/APOE KO, Tg(GFAP-APOE*4)1Hol	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)	LOAD2	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
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	human tau	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
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
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
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
PLB1-triple (hAPP/hTau/hPS1)	hAPP/hTau/hPS1, PLB1(Triple)		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
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	5xFAD^M28L		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 x 5xFAD	5xFAD^P522R		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	Plcg2*P522R x APP^NL-G-F, Plcg2^R522 x APPNL-G-F, App^NL-G-FR522	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
PS19 with humanized TREM2 (common variant)	PS19-TREM2^CV, PS19-T2^CV		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)	PS19-T2^R47H, PS19-TREM2^R47H		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
PS2APP	B6.PS2APP, TG B6.PS2APP mice (line B6.152H)	Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz	C57BL/6	APP, PSEN2	APP K670_M671delinsNL (Swedish), PSEN2 N141I	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)	PS2(N141I) x APPswe , hPS2(N141I) x hAPPswe	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	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
PS/APP	PS1 + APP, PSAPP, APP/PS1, APP/PS1 double transgenic		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
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
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
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
TASTPM (TAS10 x TPM)	TAS10 x TPM, APPswe x PS1.M1466V, TAS/TPM		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
TauPS2APP	Triple transgenic, 3Tg	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	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
Tg2576/Tau(P301L) (APPSwe-Tau)	APPSwe-Tau, APPSwe(2576)/TauJNPL3, TAPP	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
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
TREM2-BAC X 5xFAD	BAC-TREM2 X 5xFAD		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-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)	CV⁺mTrem2^−/−, CV-KO, TREM2^CV		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	CV⁺mTrem2^−/−5XFAD		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)	R47H⁺mTrem2^−/−, R47H-KO, TREM2^R47H		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	R47H⁺mTrem2^−/−5XFAD		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-IPDxAPP23xPS45	TREM2-IPDxAPP23xPS45, APP23xPS45xIPD		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) x 5XFAD	Trem2^-/-5XFAD, mTrem2^-/-5XFAD	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	Trem2^-/-PS19	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 (KOMP) x APPPS1	APPPS1;Trem2^-/-	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	hTau;Trem2^−/−	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 R47H KI (Lamb/Landreth) X APPPS1-21	APPPS1-21;Trem2^+/R47H		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)	LOAD1, APOE4/Trem2R47H, APOE4/Trem2R47H, APOE4.Trem2R47H	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
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

64 Visualizations

AD-related Research Models

Phenotypes Examined

Plaques
Tangles
Neuronal Loss
Gliosis
Synaptic Loss
Changes in LTP/LTD
Cognitive Impairment

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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/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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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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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(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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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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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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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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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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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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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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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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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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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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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 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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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	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	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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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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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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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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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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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	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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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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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 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-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) 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 (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 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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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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Search Results

67 Models

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AD-related Research Models

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 24

Gliosis at 8

Synaptic Loss at 16

Changes in LTP/LTD at 24

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

Absent

No Data

Plaques at

Tangles at

Neuronal Loss at

Gliosis at

Synaptic Loss at

Changes in LTP/LTD at

Cognitive Impairment at

Observed

Absent

No Data

Plaques at

Tangles at

Neuronal Loss at

Gliosis at

Synaptic Loss at

Changes in LTP/LTD at

Cognitive Impairment at

Observed

Plaques at 24

Gliosis at 25

Cognitive Impairment at 60

Absent

No Data

Tangles at

Neuronal Loss at

Synaptic Loss at

Changes in LTP/LTD at

Observed

Plaques at 26

Gliosis at 39

Cognitive Impairment at 13

Absent

Tangles at

No Data

Neuronal Loss at

Synaptic Loss at

Changes in LTP/LTD at

Observed

Plaques at 11

Neuronal Loss at 23

Gliosis at 11

Synaptic Loss at 24