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102 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathological
Phenotype
Cognition/ Behavior Other Phenotype Availability Primary Paper Visualization
Mouse Models (102)
3xTg-AD, The LaFerla mouse B6;129-Psen1<tm1Mpm> Tg(APPSwe,tauP301L)1Lfa/Mmjax (129X1/SvJ x 129S1/Sv)F1-Kitl<+> APP, PSEN1, MAPT APP KM670/671NL (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. APP: Transgenic; PSEN1: 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 APP/PS1, Tg6799, Tg-5xFAD B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax (C57BL/6 x SJL)F1 APP, PSEN1 APP KM670/671NL (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 2) 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 and reduced anxiety. The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live Oakley et al., 2006 Yes
Dan-amyloid, BRI2-Danish, ADan precursor protein C57BL/6J BRI2 BRI2: Familial Danish Dementia (FDD) duplication Transgenic mice with human BRI2 gene containing the Familial Danish Dementia (FDD) mutation under the control of the Syrian hamster prion protein promoter. The FDD mutation is a 10-nucleotide duplication in the region of the stop codon in the BRI2 gene, resulting in a C-terminally elongated protein. BRI2: Transgenic Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present. Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype. Adult mice fail to gain weight with age. Alopecia. Kyphosis. Available through Mathias Jucker. Coomaraswamy et al., 2010 Yes
Amyloid β (A4) precursor-like protein 2 knock-out, APLP2 KO B6.129S7-Aplp2tm1Dbo/J 129S7,C57BL/6J; backcrossed to C57BL/6J APLP2 Inactivation of the mouse APLP2 gene by deleting a 1.1kb region containing the promoter and exon 1 using a targeting vector containing a PGK-neomycin expression cassette for positive selection and a MC1-TK cassette for negative selection. APLP2: Knock-Out Alzheimer's Disease Not observed. Not observed. Homozygous animals are viable, normal in size, fertile, and do not display any gross physical or behavioral abnormalities up to 22 months of age. No impairments in axonal outgrowth of olfactory neurons following bulbectomy. The Jackson Lab: Stock# 004142; Cryopreserved von Koch et al., 1997 No
APOE2 KI C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE2 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. 2-fold higher level of steady state APOE in brain and higher APOE in serum compared with APOE3 and APOE4 KI animals. Highest levels of serum cholesterol and triglycerides after a 6hr fast. No longer available through Bruce Lamb. Mann et al., 2004 No
APOE2 Humanized Knock-in B6.129P2-Apoetm1(APOE*2)Mae N9 C57BL/6 APOE Targeted gene replacement of the endogenous murine APOE gene with the human APOE2 allele. Targeting construct included exons 2-4 of APOE2. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Characteristics of type III hyperlipoproteinemia. Plasma cholesterol and triglyceride levels 2-3x higher than APOE3 mice. Impaired clearance of very-low-density lipoprotein (VLDL) particles. Atherosclerotic plaques. Taconic: Stock# 1547-F and 1547-M Sullivan et al., 1998 No
APOE3 KI C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE3 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. Intermediate brain APOE and serum cholesterol levels compared with mice with knock-in of APOE4 or APOE2. No longer available through Bruce Lamb. Mann et al., 2004 No
APOE3 Humanized Knock-in B6.129P2-Apoetm2(APOE*3)Mae N8 129 x C57BL/6; back-crossed to C57/BL6 APOE Targeted replacement of the endogenous mouse APOE gene with the human APOE3 allele. Targeting vector contained exons 2-4 of human APOE3. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. On a standard diet, homozygous mice have normal cholesterol and triglyceride levels, but are more susceptible than wild-type animals to diet-induced atherosclerosis. Taconic: Stock# 1548-F and 1548-M Sullivan et al., 1997 No
APOE4 KI C57BL/6; 129P2, backcrossed to C57BL/6J APOE The human APOE4 cDNA sequence was knocked-in at the endogenous mouse APOE locus; inserted in frame with non-coding sequences, exon 1, intron 1 and the first 18 bp of exon 2 such that expression is regulated by endogenous regulatory elements and the mouse APOE gene inactivated. APOE: Knock-In Alzheimer's Disease, Traumatic Brain Injury Unknown. Unknown. Human ApoE is detectable in serum and astrocytes. Compared to mice with knock-in of APOE2 or APOE3, APOE4 mice had the lowest serum cholesterol after a 6 hour fast. No longer available through Bruce Lamb. Mann et al., 2004 No
APOE4 Humanized Knock-in B6.129P2-Apoetm3(APOE*4)Mae N8 129 x C57BL/6, back-crossed to C57BL/6 APOE Targeted replacement of the endogenous murine APOE gene with the human APOE4 allele; targeting construct contained exons 2–4 of APOE4. APOE: Knock-In Alzheimer's Disease Unknown. Unknown. Increased risk of atherosclerosis. Elevated cholesterol, APOE, and APOB-48 on a high fat diet. Taconic: Stock# 1549-F or 1549-M Knouff et al., 1999 No
APOE KO, APOE -/-, APOE TM1 B6.129P2-Apoetm1Unc N11 129 x C57BL/6 APOE Inactivation of the endogenous mouse APOE by homologous recombination and insertion of a neomycin cassette. APOE: Knock-Out Alzheimer's Disease Unknown. Unknown. Viable; healthy. Undetectable ApoE protein in plasma. Plasma cholesterol 5x higher than wild-type. Artherosclerotic lesions which progress to occlusions of coronary artery by 8 months. Taconic: Stock# APOE-M and APOE-F Piedrahita et al., 1992 No
B6-Tg/Thy1APP23Sdz C57BL/6 APP APP KM670/671NL (Swedish) Transgene containing human APP (isoform 751) containing the Swedish (KM670/671NL) mutation under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages. Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages. Hyperactivity observed between the ages of 6 weeks to 6 months. It is not known whether this persists or resolves in older animals. Abnormalities in open field test and impaired performance on rotorod observed from 3 months. Available through Material Transfer Management at Novartis. Sturchler-Pierrat et al., 1997 Yes
APP(SL)PS1KI, APPxPS1-Ki, APPSL/PS1KI, APP(SL)/PS1(KI) 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 KM670/671NL (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 thioflavine-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
tg13592 C57BL/6 x DBA/2 APP Transgene consisting of the signal plus 99-amino acid carboxyl-terminal sequence (SbC) of APP under the control of a cytomegalovirus enhancer/β-actin promoter. APP: Transgenic Alzheimer's Disease No neuropathology up to age 29 months; however, pathology reminiscent of inclusion body myopathy observed at 6-12 months: Aβ-immunoreactive deposits in skeletal muscle fibers. Muscle fibers with Aβ-immunoreactive deposits increased with age and also became vacuolated. Hypoactivity. The acquisition of place learning in the Morris water maze task was impaired. Higher cytochrome oxidase activity in thalamic nuclei. High levels of Aβ peptides in the plasma. Available through Ken-ichiro Fukuchi, University of Illinois College of Medicine at Peoria Fukuchi et al., 1996 No
APP-Dutch, Tg-APP(Dutch), APP E693Q, APP Dutch C57BL/6J-Tg(Thy1-APPDutch) C57BL/6J APP APP E693Q (Dutch) Transgenic mice with human APP751 bearing the E693Q mutation under the murine Thy1 promoter. APP: Transgenic Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed.  Unknown. Available through Mathias Jucker. Herzig et al., 2004 Yes
APP KI, line ADF Strain of origin: (129X1/SvJ x 129S1/Sv)F1-Kitl<+>; C57BL/6 and maintained on a mixed background APP APP KM670/671NL (Swedish), APP V717I (London), APP E693Q (Dutch) Knock-in of wild-type mouse APP exon 16 (truncated after residue KM), FLAG tag (2 repeats), a stop codon, a poly A signal region from the human growth hormone gene and an additional copy of exon 16 carrying the Swedish mutation and a modified exon 17 with the London and Dutch mutations. APP: Knock-In Alzheimer's Disease Unknown. Unknown. The Jackson Lab: Stock# 008390; Cryopreserved No
APP null, APP KO B6.129S7-Apptm1Dbo/J C57BL/6J APP Inactivation of the mouse APP gene by replacing a 3.8 kb sequence encoding the promoter and exon 1 with a neomycin resistance cassette. APP: Knock-Out Alzheimer's Disease Elevated reactive gliosis by 14 weeks in the hippocampus and parts of the neocortex. Impaired spatial learning as measured by the water maze at 4 and 10 months. Hypoactivity and decreased locomotor activity and forelimb grip strength. Homozygous knock-out mice weigh 15-20% less than age-matched wild-type mice. The Jackson Lab: Stock# 004133; Live Zheng et al., 1995 No
APP NL-F/NL-F C57BL/6 APP APP KM670/671NL (Swedish), APP I716F Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and the Swedish and Beyreuther/Iberian mutations. APP: Knock-In Alzheimer's Disease Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. No overexpression of APP. Generates wild-type levels of AICD. Available through Takaomi Saido. Saito et al., 2014 Yes
APP NL-G-F/NL-G-F C57BL/6 APP APP KM670/671NL (Swedish), APP I716F, APP E693G (Arctic) Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and three pathogenic mutations (Swedish, Beyreuther/Iberian, and Arctic). APP: Knock-In Alzheimer's Disease Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 6 months as measured by the Y maze. No overexpression of APP. Wild-type levels of AICD. Available through Takaomi Saido. Saito et al., 2014 Yes
APPPS1-21 B6-Tg(Thy1-APPswe; Thy1-PS1 L166P) C57BL/6J APP, PSEN1 APP KM670/671NL (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
Tg2576;Pdgfrβ+/- APPsw mice on C57BL/6; Pdgfrβ+/- mice on 129S1/SvlmJ. APP, PDGFRB APP KM670/671NL (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/NOS2 bigenic mice, APPSDI/NOS2KO, CVN B6.Cg-Nos2tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/Mmjax C57BL/6J; C57BL/6N APP, NOS2 APP KM670/671NL (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
APPSw, hAPPSwe (line 71) , hAPPSwe (line 72), huAPPSw B6.D2-Tg(Thy1-APPSwe)71Blt; B6.D2-Tg(Thy1-APPSwe)72Blt C57BL/6, DBA/2, crossed to C57BL/6 APP APP KM670/671NL (Swedish) Transgene with human APP751 with the Swedish mutation driven by the Thy1.2 promoter. APP: Transgenic Alzheimer's Disease Amyloid plaques by 17-18 months in the neocortex and hippocampus with detection of 5-10 fold more Aβ40 than Aβ42. Plaque burden significantly lower than in the double transgenic PS2APP. Lower levels of insoluble Aβ40 and Aβ42 than the PS2APP mouse at 16-18 months. Unknown. Available through Laurence Ozmen. Richards et al., 2003 No
R1.40, APP(K670/M671), R1.40-YAC B6.129-Tg(APPSw)40Btla/Mmjax (129X1/SvJ x 129S1/Sv)F1-Kitl<+> APP APP KM670/671NL (Swedish) A 650 kb YAC transgene containing the entire human APP gene and ~250 kb of flanking sequence was mutated to include the Swedish mutation (K670N/M671L). Founder animals (line R1.40) were backcrossed to C57BL/6J. APP: Transgenic Alzheimer's Disease By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months. Unknown. Increased mortality in young homozygous animals, especially females. At 3-4 months mice maintained on the C57BL/6J background exhibit spontaneous seizure-like activity as measured by EEG and are more susceptible to kainic acid-induced seizures. The Jackson Lab; available through the JAX MMRRC Stock# 034831; Cryopreserved Lamb et al., 1997 Yes
APP(695)Swe C3B6-Tg(APP695)3Dbo/Mmjax C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J APP APP KM670/671NL (Swedish) Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain and the Swedish mutation under the control of the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Age-associated increase in Aβ40 and Aβ42 and some amyloid deposition at advanced age. Congenic animals showed normal reference and working memory up to 12-14 months. The Jackson Lab; available through the JAX MMRRC: Stock# 034828; Cryopreserved Borchelt et al., 1996, Savonenko et al., 2003 No
B6.Cg-Tg(Prnp-App/APPswe)E1-2Dbo/Mmjax C3H/HeJ x C57BL/6J; backcrossed to C57BL/6J APP APP KM670/671NL (Swedish) Transgene is a chimeric mouse/human APP (isoform 695) with a "humanized" Aβ domain carrying the Swedish mutation under the control of the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Age-dependent increase in Aβ42, with low levels at 6-14 months and high levels at 24-26 months. No cognitive impairment in tasks of reference or working memory at 12-14 months. More than half of the female hemizygous mice do not survive past 15 months of age. The Jackson Lab; available through the JAX MMRRC Stock# 034835; Cryopreserved Savonenko et al., 2003, Borchelt et al., 1996 No
APP YAC Swe/Lon (line J1.96), B6-J1-96 B6.129S4-Tg(APPSwLon)96Btla/Mmjax 129S4/SvJae-derived J1 ES cells; backcrossed to C57BL/6 APP APP KM670/671NL (Swedish), APP V717I (London) A 650 kb YAC transgene containing the entire human APP gene carrying the Swedish and London mutations with ~ 250 kb of flanking sequence; founder animals (line J1.96) have a single copy of the transgene. APP: Transgenic Alzheimer's Disease No amyloid plaques observed at 2 years. Unknown. The Jackson Lab; available through the JAX MMRRC Stock# 034837; Cryopreserved Lamb et al., 1997 No
APPSwe (line C3-3)/PSEN1(A246E), APP/PS1 B6C3-Tg(APP695)3Dbo Tg(PSEN1)5Dbo/J Origin: (C57BL/6J x C3H/HeJ)F2 APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 A246E Double transgenic mice; cross of mice expressing the human PSEN1 gene with the A246E mutation under the control of the mouse prion protein promoter with mice expressing chimeric APP (isoform 695) with the Swedish mutation also under the control of the mouse prion promoter. The chimeric APP molecule was created by replacing the mouse Aβ sequence with the cognate human sequence. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Elevated Aβ42(43) peptide in the brain. By 9 months develop amyloid deposits in the cortex and hippocampus which become more numerous by 10-12 months. Dystrophic neurites associated with gliosis in the cortex and hippocampus. Aβ42 and Aβ40 codeposit. Poor nest building. Reduced retention on learned passive avoidance task. Increased immobility time in forced swim task. Increased irritability. The Jackson Lab: Stock# 003378; Cryopreserved Borchelt et al., 1997, Borchelt et al., 1996 Yes
APP/PS1, APPswe/PS1deltaE9, line 85, APP(swe) + PSEN1DeltaE9 B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax C57BL/6 x C3H)F2 APP, PSEN1 APP KM670/671NL (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 promotor elements. The two transgenes co-integrated and co-segrate 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. Impairment in the Morris water maze at 12 months. High incidence of seizures. High incidence of seizures. Tail phenotype that is believed to be due to genetic background. The Jackson Lab; available through the JAX MMRRC Stock# 034829; Live Jankowsky et al., 2001, Jankowsky et al., 2004 Yes
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 KM670/671NL (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; Live Savonenko et al., 2005 No
NSE-APPsw Origin: C57BL/6 x DBA/2 APP APP KM670/671NL (Swedish) Transgene containing human APP (isoform 695) bearing the Swedish mutation under the control of neuron specific enolase (NSE) promoter. APP: Transgenic Alzheimer's Disease Increased Aβ42 in the cortex and hippocampus of 12 month old mice, but no plaques. Increased tau phosphorylation and TUNEL-stained nuclei relative to control mice. In water maze tests, 12 month old mice had longer escape latencies than age-matched control mice. Metallothionein expression was increased in brain astrocytes and was thought to attenuate Aβ-induced neurotoxicity.  Increased Cox-2 and caspase-3 compared to age-matched control mice.   Available through Yong K Kim.       Hwang et al., 2004 No
Knock-in of APP(V642I) Origin:C57BL/6 x CBA; chimeric mice breed to CD-1 mice APP APP V717I (London) Targeted knock-in of the V642I mutation into exon 17 of the mouse APP gene using homologous recombination and the Cre-loxP system. APP: Transgenic Alzheimer's Disease Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy. At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels. Unknown. Kawasumi et al., 2004 Yes
APPlon, APP-london, APPLd, APP-ld, APP(V717I), APP[V717I], APP.V717I, APP(London) (line 2), APP/LD/2 Thy1-hAPP.V717I (C57BL/6.FVB/N) Originally generated on FVB/N background; available at reMYND as C57BL/6xFVB/N APP APP V717I (London) Transgene containing human APP (isoform 695) with the London mutation driven by the Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology. From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression. Increased mortality (72% by day 180). Increased incidence of seizures. Available through the KU Leuven Research and Development Office and reMYND. Moechars et al., 1999 Yes
APPxPS1, APP(V717I)x PS1(A246E), APP[V717I]x PS1[A246E], APP.V717I x PS1.A246E Thy1-hAPP.V717I ( C57BL/6)x Thy1-hPS1.A246E (FVB/N) 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. Available through reMYND. Dewachter et al., 2000 Yes
APPSw/Ind/Arc, APPSwedish/Indiana/Arctic, hAPP Arc line Inbred C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana), APP E693G (Arctic) A human APP minigene with the Swedish, Indiana, and Arctic mutations driven by the platelet-derived growth factor β-chain promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20. At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform. Premature lethality. Trend toward hyperactivity. Reduced calbindin and Fos levels in the dentate gyrus. Cryopreserved. Contact Lennart Mucke Cheng et al., 2004 Yes
arcAbeta Origin: B6D2 F1 APP APP KM670/671NL (Swedish), APP E693G (Arctic) Human APP695 transgene containing the Swedish (K670N/M671L) and Arctic mutation (E693G) was generated by site-directed mutagenesis. APP: Transgenic Alzheimer's Disease At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma. Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze. Unknown. Knobloch et al., 2007 Yes
BACE1 -/-, BACE1 KO B6.129-Bace1tm1Pcw/J C57BL/6J BACE1 Homologous recombination was used to disrupt a 2kb section of BACE1 containing exon 1 replacing it with a neomycin selection cassette and the HSV thymidine kinse gene. BACE1: Knock-Out Alzheimer's Disease Hypomyelination in the hippocampus and cerebral cortex, but normal axonal development. Increased thermal pain sensitivity as measured by a hot plate test. Decreased grip strength. Homozygous mice are viable, fertile, normal in size. No BACE1 protein is detected by Western blot. Primary cultures of cortical neurons do not secrete Aβ1-40/42, Aβ11-40/42 or β-C terminal fragments (β-CTFs). The Jackson Lab: Stock# 004714; Live Cai et al., 2001 No
BACE2delta6, BACE2 KO B6;129P2-Bace2tm1Bdes/J Strain of origin: 129P2/OlaHsd BACE2 Cre mediated recombination was used to remove exon 6 of BACE2. A targeting vector containing a loxP site and hygromycin resistance gene flanked by FRT sites was introduced into intron 5 and a second loxP site was inserted within intron 6. Heterozygous mice were crossed with mice expressing Cre under the ubiquitous phosphoglycerate kinase promoter to delete exon 6 in progeny. BACE2: Knock-Out Alzheimer's Disease Not observed. Not observed. BACE2 deficient fibroblasts produced higher levels of Aβ compared with wild-type cells. The Jackson Lab: Stock# 005618; Cryopreserved Dominguez et al., 2005 No
BRI2-Aβ40 B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J B6C3, backcrossed to C57BL/6J to generate congenic strain Construct encodes a fusion protein of the BRI protein and Aβ40 driven by the mouse prion promoter; Aβ40 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ40. Transgenic Alzheimer's Disease No overt amyloid pathology or detergent-insoluble amyloid-β. Hemizygous mice on a mixed background (C57/B6//C3H) have intact cognition as measured by fear conditioning at 12 and 14-17 months. The Jackson Lab: Stock# 007180; Cryopreserved McGowan et al., 2005 No
BRI2-Aβ42, BRI-Abeta42 B6.Cg-Tg(Prnp-ITM2B/APP695*42)A12Emcg/J B6C3, backcrossed to C57BL/6J to generate congenic strain Construct encodes a fusion protein of the BRI protein and Aβ42 driven by the mouse prion promoter. Aβ42 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ42. Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss. On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid. The Jackson Lab: Stock# 007182; Cryopreserved McGowan et al., 2005 Yes
fPS1/fPS1Δ;Nestin-Cre (PS1 cKO) C57BL6/129 PSEN1 PS1 inactivation in neuronal progenitor cells (NPCs) and NPC-derived neurons and glia was achieved by crossing a floxed PS1 mouse with a Nestin-Cre transgenic mice. PSEN1: Conditional Knock-out Alzheimer's Disease Premature differentiation of neural progenitor cells results in reduced cells and neurons. 45 percent of late-born neurons fail to migrate to their appropriate positions in the superficial cortical layers. Gross behavior deficits. Mice are small. Premature death at 2-3 months of age. Available through Jie Shen. Wines-Samuelson et al., 2005 No
APOE4 (line1)/APOE KO, Tg(GFAP-APOE*4)1Hol 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; Live Sun et al., 1998 No
C57B6/C3H BACE1 Transgene of human BACE1 driven by the prion protein (PrP) promoter. BACE1: Transgenic Alzheimer's Disease No evidence of Aβ deposition in single transgenic animals. Unknown. Unknown. Lee et al., 2005 No
C57BL/6 J BACE1 Wild-type human BACE driven by the murine Thy1 promoter. BACE1: Transgenic Alzheimer's Disease Not observed. Unknown. Decreased levels of full-length mature APP and increased levels of C99 and C89. Human BACE mRNA 4x higher than endogenous murine BACE. Highest expression of human BACE protein in cortex and hippocampus, lowest in cerebellum. Available through Material Transfer Management at Novartis. Bodendorf et al., 2002 No
human tau B6.Cg-Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/J The targeted allele was created in 129S4/SvJae-derived J1 embryonic stem cells which 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 backcrossed 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 backcrossed 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 4 months, but were 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). Jackson Labs: Stock# 005491; Live Andorfer et al., 2003 Yes
Tau.P301S, hTAU[P301S], tau[P301S] Thy1-hTau.P301S (CBA.C57BL/6) CBAxC57BL/6 MAPT MAPT P301S Transgenic mice overexpressing a human tau isoform 383 amino acids long with 4 microtubule-binding repeat domains and without N-terminal inserts (4R/0N). Site-directed mutagenesis was used to introduce the P301S mutation. Transgene is under the control of the neuron-specific murine Thy-1 promoter. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tangle like pathology in the cerebral cortex, hippocampus, brain stem and the spinal cord. Neurodegeneration, especially in the spinal cord, which is accompanied by astrocytosis. Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2-3 months. Muscle weakness, tremor. Frequent eye inflammation. Available through reMYND. Allen et al., 2002 Yes
C57BL BACE1 Transgene expressing wild-type human BACE1 driven by the mouse Thy1 promoter. BACE1: Transgenic Alzheimer's Disease Not observed. Unknown. Transgene expressed in neurons only. No change in processing of endogenous murine APP. No longer available through Michael Willem. Willem et al., 2004 No
PDGF-APPSw,Ind, PDGF-hAPP695,751,770V171F, KM670/671NL, hAPPJ20, Mucke mice B6.Cg-Tg(PDGFB-APPSwInd)20Lms/2Mmjax (C57BL/6 x DBA/2)F2 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. APP: Transgenic Alzheimer's Disease Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptophysin immunoreactvity. Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated. On the C57BL/6J background hippocampal hyperexcitability was observed and cortical and hippocampal spontaneous nonconvulsive seizures. The Jackson Lab; available through the JAX MMRRC Stock# 034836; Live Mucke et al., 2000 Yes
TauP301L-JNPL3 Tg(Prnp-MAPT*P301L)JNPL3Hlmc C57BL/6, DBA/2, SW Mixed Background MAPT MAPT P301L Transgene for human MAPT (4R0N) with the P301L mutation driven by the mouse prion promoter. MAPT: Transgenic Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord. By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization. Eye irritiation, possibily due to carrying the Pde6brd1 retinal degeneration mutation carries Pde6brd1 mutation Taconic: Stock#2508 (homozygote), #1638 (heterozygote and wild-type) Lewis et al., 2000 Yes
hAPPSL, hAPP-SL, AβPP751, TASD41, mThy1-hAβPP751 Swe Lon (line 41), APP751SL, hAPPlon/swe line 41 , APP41 mThy1-hAβPP751 Swe Lon C57BL/6 x DBA APP APP KM670/671NL (Swedish), APP V717I (London) The transgene over-expresses the mutant human amyloid protein precursor (751 isoform), which bears both the Swedish (K670N/M671L) and the London (V717I) mutations, under the control of the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region. Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration. Available through Eliezer Masliah. A similar strain, APPSL, is available through QPS-Austria on a congenic C57BL/6 background. Rockenstein et al., 2001 Yes
Origin: C57BL/6J; backcrossed with murine APOE-null mice APOE ApoE3 minigene driven by the rat neuron-specific enolase promoter. APOE: Transgenic Alzheimer's Disease Human ApoE3 protected against the age-dependent neurodegeneration seen in APOE -/- mice. Unknown. Widespread neuronal expression of ApoE in the brain. Expression of ApoE3 protected against kainic acid-induced neuronal damage (loss of synaptophysin-positive presynaptic terminals and MAP2-positive neuronal dendrites in the neocortex and hippocampus, and a disruption of neurofilament-positive axons in the hippocampus). Available through Robert Mahley. Raber et al., 1998 No
Origin: C57BL/6J; backcrossed with murine ApoE-null mice APOE The ApoE4 minigene driven by the rat neuron-specific enolase promoter. APOE: Transgenic Alzheimer's Disease Not observed. NSE-ApoE4 mice showed impairments in learning a water maze task and in vertical exploratory behavior that increased with age and seen primarily in females. Neuronal ApoE expression was widespread in the brain. Expression of ApoE4 did not protect against kainic acid-induced neuronal damage. Available through Robert Mahley. Raber et al., 1998 No
C57BL/6× DBA/2 PSEN2 PSEN2 N141I (Volga German) Transgene containing human PSEN2 carrying the N141I mutation driven by the neuron-specific enolase (NSE) promoter. PSEN2: Transgenic Alzheimer's Disease Not observed. Behavioral deficits in the water maze at 12 months in mice expressing mutatnt as well as wild-type PSEN2, including longer escape latencies than wild-type mice, but no difference in swimming speed. Expression of PSEN2 was higher in mice expressing mutant as well as wild-type PSEN2 compared to age-matched, non-transgenic mice. Alterations in levels of Aβ42, caspase-3 and Cox-2 proteins. Unknown. Hwang et al., 2002 No
hAPP695Indiana, elan mouse, PDAPP, PD-APP C57B6 x DBA2 APP APP V717F (Indiana) A PDGF-driven human APP minigene with the V717F (Indiana) mutation. The construct contained APP introns 6-8 allowing alternative splicing of exons 7 and 8. APP: Transgenic Alzheimer's Disease Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus. Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months. Alterations in sleep/wake states, thermoregulation, and motor activity.   Unknown. Games et al., 1995, Rockenstein et al., 1995 Yes
APP(Swedish,Indiana), line J9, hAPPJ9 C57BL/6 x DBA/2 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Transgene expresses human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations under the control of the human platelet derived growth factor-β (PDGF-β) promoter. APP: Transgenic Alzheimer's Disease Amyloid plaques at 8-10 months, but not at 2-4 months when deficits in synaptic transmission are observed. Approximately 20% of mice had plaques at 5-7 months, 50% at 8-10 months, and 100% by 21-25 months. Unknown Deficits in synaptic transmission at 2-4 months, prior to amyloid deposition. Available through Lennart Mucke. Hsia et al., 1999 No
line I5 B6.Cg-Tg(PDGFB-APP)5Lms/J (C57BL/6 x DBA/2)F2 APP APP-WT driven by the human PDGF-β promoter; an APP transgene with the Indiana mutation was converted to wild-type by PCR primer modification. APP: Transgenic Alzheimer's Disease Expression of human APP in the brain especially in the neocortex and hippocampus. No plaques up to 24 months. Unknown. The Jackson Lab: Stock# 004662; Cryopreserved Mucke et al., 2000 No
hBACE1 C57BL/6J, for at least six generations BACE1 Targeted insertion of a single copy of human BACE1 at the HPRT locus on the X chromosome. Transgene expression driven by the mouse CaMKII-α promoter. BACE1: Transgenic Alzheimer's Disease Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology. Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety. Breeding, litter size, and overall health are normal. Reduced body weight in knock-in animals after six months of age in males and nine months in females. Available through Bettina Platt Plucińska et al., 2014 Yes
APP(Prnp), line A-2 B6.Cg-Tg(Prnp-APP)A-2Dbo/J C57BL/6 APP Transgene expresses human APP driven by the mouse prion protein promoter. APP: Transgenic Alzheimer's Disease Unknown. Unknown. Jackson Labs: Stock# 006006; Cryopreserved No
FVB/N PSEN1 PSEN1 A246E Transgene human PSEN1 with the A246E mutation driven by the mouse Thy1 promoter. PSEN1: Transgenic Alzheimer's Disease Histologically normal up to 2 years old by hematoxylin-eosin, silver, and thioflavin-S staining. Learning and spatial memory were unaffected in the water maze test. Neither the escape latency nor escape pathway was different from PSEN1 wild-type mice at 1 and 9 months of age. Mice are more sensitive to kainic acid displaying greater KA-induced seizure activity and neuronal damage. LTP induced by a strong stimulus was not altered, but a weak stimulation at synapses between Schaeffer’s collaterals and CA1 pyramidal neurons elicited LTP only in mutant mice. No longer available through Paul van Dun. Schneider et al., 2001 No
PS1 conditional KO, PSEN1 conditional KO fPS1/fPS1;αCaMKII-Cre CaM-Cre tg mice were generated in C57BL/6J x CBA hybrid, and then back-crossed several generations to C57BL/6J. The floxed PS1 mouse was generated in C57BL/6J and 129/Sv hybrid. PSEN1 PS1 conditional KO mice with selective deletion of PSEN1 in excitatory neurons of the forebrain beginning about 1 month of age post-natally were generated by crossing a floxed PS1 mouse with a CamKII-Cre transgenic mouse. PSEN1: Conditional Knock-out Alzheimer's Disease Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments. Subtle but significant deficits in long-term spatial memory in the Morris water maze. Available through Jie Shen. Yu et al., 2001 Yes
PSEN1(M146L), PS1 (M146L) line 5.1 Swiss Webster x B6D2F1 PSEN1 PSEN1 M146L (A>C) Transgene containing human PSEN1 with the M146L mutation driven by the rat PDGF-β promoter. PSEN1: Transgenic Alzheimer's Disease No abnormal pathology up to 2.5 years. Elevated Aβ2(43); no effect on Aβ40. Altered mitochondrial activity. Disregulation of calcium homeostasis. No difference from wild-type mice in the “Y” maze (alternation performance or activity) at 12-14 weeks. Elevated PSEN1 expression (2-3 fold). Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with wild-type mice. Larger calcium responses to depolarization. Stronger synaptic potentiation of the CA3 to CA1 projection. Available through the Technology Transfer Office, Patents & Licensing, University of South Florida. Duff et al., 1996 No
PSEN1(M146V) (line 8.9) Swiss Webster x B6D2F1 PSEN1 PSEN1 M146V Transgene containing human PSEN1 with the M146V mutation driven by the rat PDGF-β promoter. PSEN1: Transgenic Alzheimer's Disease No abnormal neuropathology up to 2.5 years. Elevated Aβ42(43). Altered mitochondrial activity and disregulation of calcium homeostasis. Unknown. Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with nontransgenic or mice transgenic for wild-type PSEN1. Available through the Technology Transfer Office, Patents & Licensing, University of South Florida. Duff et al., 1996 No
PS-1 P264L knock-in R1 line of the ES cells (129 mouse strain) PSEN1 PSEN1 P264L An exon replacement strategy was used to generate mouse lines carrying a targeted mutation in their endogenous presenilin-1 gene. A proline-to-leucine substitution was targeted to codon 264 in exon 8 by homologous recombination in embryonic stem (ES) cells. Cre-lox system to remove the neomycin selection cassette from the targeted gene. PSEN1: Knock-In Alzheimer's Disease Not observed. Unknown. Unknown. Siman et al., 2000 No
B6.PS2APP, TG B6.PS2APP mice (line B6.152H) Tg(Thy1-APPSwe,Prnp-PSEN2*N141I)152HLaoz C57BL/6 APP, PSEN2 APP KM670/671NL (Swedish), PSEN2 N141I (Volga German) 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
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 KM670/671NL (Swedish), PSEN2 N141I (Volga German) 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
Prp-huPS2(N141I), PS2-N141I (line 30), hPS2mut Tg(Prnp-PSEN2*N141I)30Jgr Originally generated in a B6.D2 background, then crossed into C57BL/6J. PSEN2 PSEN2 N141I (Volga German) Human PSEN2 gene with the N141I mutation driven by the mouse prion protein promoter. PSEN2: Transgenic Alzheimer's Disease Unknown. Unknown. Ubiquitous expression of mutant transgene. Brain homogenate from 2 week-old mice had PSEN levels 1.8-2.2 fold higher than wild-type mice. Disrupted Ca2+ homeostasis, similar to that of double transgenic PS2APP mice, including a reduction in endoplasmic reticulum Ca2+ content in cultured neurons and a generally decreased response to metabotropic agonists. Available through Laurence Ozmen. Richards et al., 2003 No
PS1 + APP, PSAPP Swiss Webster, B6D2F1, C57Bl/6SJL, C57Bl/6 APP, PSEN1 APP KM670/671NL (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 mice are available through Taconic (Stock #001349) and Charles River. The PS1(M146L) line is available through the Technology Transfer Office, Patents & Licensing, University of South Florida. Holcomb et al., 1998 Yes
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
PS1 conditional KO B6;129P-Psen1tm1Vln/J Origin: 129P2/OlaHsd; backcrossed to C57BL/6 PSEN1 A targeting vector containing a neomycin resistance gene was inserted downstream of exon 7 of PSEN1; loxP sites were inserted on both sides of exon 7 and downstream of the neomycin resistance gene. PSEN1: Knock-Out Alzheimer's Disease No morphological abnormalities. When crossed with Cre recombinase driven by Thy1, brain levels of Aβ40 and Aβ42 decrease and C-terminal fragments of APP accumulate. When crossed with Cre recombinase driven by Thy1, no cognitive deficit in an object recognition task. When crossed with Cre recombinase driven by Thy1, LTP induction is slightly altered. The Jackson Lab: Stock# 007605; Cryopreserved Dewachter et al., 2002 No
PS1 -/-, PSEN1 null, Psen1tm1Shn, PS1 null B6.129-Psen1tm1Shn/J C57BL/6 PSEN1 A targeting construct containing a neomycin cassette was used to disrupt exons 2 and 3 of the endogenous mouse PS1 gene. PSEN1: Knock-Out Alzheimer's Disease Impaired neurogenesis. Massive neuronal loss. Hemorrhages in the CNS. Unknown. Homozygous mice die shortly after birth; heterozygous mutants are viable and fertile. Gross skeletal malformations. The Jackson Lab: Stock# 003615; Cryopreserved Shen et al., 1997 No
PS1M146V KI B6.129-Psen1tm1Mpm/J C57BL/6 PSEN1 PSEN1 M146V Point mutations were introduced into exon 5 of the endogenous mouse PSEN1 gene altering the codons corresponding to amino acids 145 and 146 from isoleucine and methionine to valine and valine, respectively. The targeting vector contained a lox-P flanked neomycin resistance cassette and herpes simplex virus thymidine kinase genes. PSEN1: Knock-In Alzheimer's Disease Hypersensitive to kainate-induced degeneration and death of CA3, CA1 and hilar neurons. Cultured hippocampal neurons have increased vulnerability to death induced by glutamate. Disrupted calcium homeostasis. Increased oxidative stress and mitochondrial dysfunction. Unknown. Mice are viable, fertile, and normal in size. No gross physical or behavioral abnormalities. The Jackson Lab: Stock# 004193; Cryopreserved Guo et al., 1999 No
line 13, PS1(P117L) Mixed C57BL/6 and DBA/2J PSEN1 PSEN1 P117L Transgene of human PSEN1 with the P117L mutation driven by the neuron specific enolase (NSE) promoter. PSEN1: Transgenic Alzheimer's Disease No plaques or diffuse amyloid deposits at 2-3 months. Elevated generation of Aβ42. Unknown. Express human PSEN1 at 2-3x the level of endogenous murine PSEN1. Impaired neurogenesis in the hippocampus. No longer available. Wen et al., 2002 No
PS1(WT), PSEN1 (wild-type) Mixed C57BL/6J, DBA/2J PSEN1 Human wild-type PSEN1 driven by neuron-specific enolase (NSE). PSEN1: Transgenic Alzheimer's Disease No pathological changes have been observed in these mice. Unknown. No longer available. Wen et al., 2002 No
line G9, H163R mutant PS-1 YAC, B6-G9, PS1-YAC B6.129S4-Tg(PSEN1H163R)G9Btla/J Origin: 129S4/SvJae, backcrossed to C57BL/6 PSEN1 PSEN1 H163R A 1000 kb YAC transgene (788H12) containing the entire human PSEN1 gene with the H163R mutation. Transgene also has ~550 kb of upstream and 350 kb of downstream flanking sequences. PSEN1: Transgenic Alzheimer's Disease Elevated Aβ42 in the brain and plasma. Higher levels and earlier Aβ deposition when crossed with APP YAC line R1.40. Unknown. Alternatively spliced human PSEN1 transcripts. The Jackson Lab: Stock# 006469; Cryopreserved Lamb et al., 1999 No
PS2 -/-, PSEN2 null, PSEN KO, PS2 null B6.129P-Psen2tm1Bdes/J 129P2/OlaHsd derived embryonic stem cells injected into C57BL/6 blastocysts; resulting chimeric mice backcrossed to C57BL/6J PSEN2 A targeting vector containing a hygromycin resistance gene driven by the phosphoglycerate kinase promoter was used to disrupt exon 5 of PSEN2 by introducing a frame shift between exons 4 and 6. PSEN2: Knock-Out Alzheimer's Disease No gross brain abnormalities or astrogliosis. Unknown. Alveolar wall thickening, pulmonary fibrosis, mild hemorrhage in the lungs. The Jackson Lab: Stock# 005617; Cryopreserved Herreman et al., 1999 No
rTg4510, Tg(tetO-TauP301L)4510, Tau P301L FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ, STOCK Tg(Camk2a-tTA)1Mmay Tg(tetO-MAPT*P301L)#Kha/J FVB/N MAPT MAPT P301L Transgene has human four-repeat MAPT lacking the amino terminal sequence (4R0N) with the P301L mutation. Expression is driven by a tetracycline operator (tetO) upstream of a cytomegalovirus minimal promoter and contains exons 2-3 of the mouse prion protein gene (Prnp) untranslated sequence. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60%) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (6 to 8 weeks) suppression of transgenic tau. No significant abnormalities at 1.3 months in the Morris Water Maze. Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months. When the transgene was suppressed with dox at 2.5 months spatial memory improved. Homozygous mice are not viable. The Jackson Lab: Stock# 015815 (single transgenic line); Live;  The Jackson Lab: Stock# 024854 (double transgenic line); In Progress Santacruz et al., 2005 Yes
SAMP8, SAMP-8, SAM-P/8, SAM-P8 AKR/J, suspected outbreeding to unknown line One of several related strains developed from an AKR/J inbred line with a spontaneous accelerated aging phenotype. Spontaneous Alzheimer's Disease Age-associated increase in hippocampal Aβ from 4 to 12 months, but no plaque-like structures by Congo red or thioflavine S. Spongiform degeneration: vacuoles of various size in the neuropil in the brain stem. Microglial cell proliferation. Degeneration of dopamine neurons in the substantia nigra and noradrenaline neurons in the locus coeruleus. Age-associated behavioral impairments including learning and memory difficulties, emotional disorders (reduced anxiety-like behavior and depressive behavior) and altered circadian rhythms of spontaneous motor activity and drinking behaviours. Harlan: SAMP8/TaHsd Yagi et al., 1988 No
Tau.P301L, hTau.P301L, Tau-4R-P301L, Tau(P301L) Thy1-hTau.P301L FVB/N MAPT MAPT P301L These transgenic mice overexpress the human Tau-4R/2N isoform bearing the P301L mutation under the control of the neuron-specific murine Thy1 promoter. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF. Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months. Premature death around 8-12 months, preceded by weight loss, hyperkyphosis, reduced activity, and upper airway dysfunction. Available through reMYND. Terwel et al., 2005 Yes
Line PS19, PS19Tg B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J (C57BL/6 x C3H)F1 MAPT MAPT P301S Transgenic line expressing mutant human tau under the direction of the mouse prion protein (Prnp) promoter. The transgene codes for tau with four microtubule-binding domains and one N-terminal insert (4R/1N). MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis. Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months. Clasping and limb retraction when lifted by the tail at three months, followed by limb weakness and brain atrophy. Homozygous females do not mate. The Jackson Lab: Stock# 008169; Live Yoshiyama et al., 2007 Yes
Triple transgenic, 3Tg B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L) C57BL/6, DBA/2; backcrossed to C57BL/6 APP, MAPT, PSEN2 APP KM670/671NL (Swedish), MAPT P301L, PSEN2 N141I (Volga German) 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
TgTauR406W B6SJL/F1; backcrossed to C57BL/6J MAPT MAPT R406W Human 4-repeat tau cDNA with the R406W mutation containing myc and FLAG tags at N-and C-terminal ends, respectively, and driven by the CaMK-II promoter. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments. Impairments in contextual and cued fear conditioning at 16–23 months compared with wild-type littermates. No detectable sensorimotor deficits. No differences from wild-type in body weight, sensorimotor reflexes (acoustic startle response), or motor coordination (accelerating rotarod and pole tests).  Attenuation of the Schaffer collateral-evoked neural response in hippocampal slices. Decrease in prepulse inhibition. Higher mortality. Unknown. Tatebayashi et al., 2002 Yes
RW Tg mice C57BL6 x C3H, maintained in B6C3 background MAPT MAPT R406W Human tau with the R406W mutation driven by the mouse prion promoter. MAPT: Transgenic Frontotemporal Dementia Age-dependent increase in tau. Neurofibrillary-tangle-like pathology (filamentous intraneuronal tau aggregates), especially in the hippocampus. Neurodegeneration. Extensive gliosis in the brain and spinal cord. Progressive motor weakness with advancing age, as demonstrated by dystonic movements of the hindlimbs when lifted by the tail. Altered microtubule binding and slow axonal transport of tau. Reduced lifespan. Unknown. Zhang et al., 2004 No
MAPT V337M, Tg214 B6SJL/F1 MAPT MAPT V337M (Seattle Family A) Human 4-repeat tau driven by the PDGF-β promoter. Tagged with myc and Flag on the N- and C-terminals respectively. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure. Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze. The amount of mutant tau varied, but was generally less than one tenth of endogenous tau levels. In hippocampal slices there was attenuation of the Schaffer collateral-evoked neural response. Unknown. Tanemura et al., 2002, Tanemura et al., 2001 Yes
Truncated beta-amyloid 42 C57BL6 APP Transgenic vector expresses a human N-terminally truncated Aβ sequence (3-42) fused to thyrotropin-releasing hormone. The transgene is under the control of the murine Thy1.2 regulatory sequence. The glutamate at position 3 of Aβ was mutated to glutamine to facilitate pyroglutamate formation by the enzyme glutaminyl cyclase. APP: Transgenic Alzheimer's Disease Intraneuronal accumulation of Aβ peptides in the hippocampus by three months and in cerebellar nuclei by six months. Marked gliosis in the hippocampus by 12 months. Very rare extracellular Aβ deposits. Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at three and six months. Early and persistent decrease in anxiety in the elevated plus maze. Comparable to wild-type in general motor coordination at three and six months as indicated by the balance-beam test, but impairment at 12 months. Available through Thomas Bayer. Wittnam et al., 2012 Yes
line 102 B6.Cg-Tg(tetO-APPSwInd)102Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest doxycycline sensitivity relative to lines 107 and 885. Hyperactivity. The Jackson Lab; available through the JAX MMRRC Stock# 034845; Cryopreserved Jankowsky et al., 2005 No
line 107 B6.Cg-Tg(tetO-APPSwInd)107Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Intermediate expression of transgene and doxycycline sensitivity relative to lines 102 and 885. Hyperactivity. The Jackson Lab; available through the JAX MMRRC Stock# 034846; Cryopreserved Jankowsky et al., 2005 No
line 885 B6C3-Tg(tetO-APPSwInd)885Dbo/Mmjax C57BL/6 x C3HeJ; backcrossed to C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Mouse APP695 with a humanized Aβ region and the Swedish (KM570/571NL) and Indiana (V617F) mutations downstream of a tetracycline-responsive promoter and mouse prion protein exons 1-2. APP: Transgenic Alzheimer's Disease APP protein 10-30x higher than endogenous mouse APP. Progressive amyloid plaques starting at 2 months. Extensive amyloid pathology by 9 months especially in the cortex and hippocampus. Amyloid pathology is halted by transgene suppression but existing plaques are stable. Highest transgene expression and highest doxycycline requirement relative to lines 102 and 107. Hyperactivity. The Jackson Lab; available though the JAX MMRRC Stock# 034834; Cryopreserved Jankowsky et al., 2005 No
Hsiao mice, App-Swe, App-sw, APP(sw) B6;SJL-Tg(APPSWE)2576Kha B6;SJL Mixed Background APP APP KM670/671NL (Swedish) The human APP gene (isoform 695) containing the double mutation K670N, M671L (Swedish mutation) under the control of the hamster prion protein. APP: Transgenic Alzheimer's Disease Numerous parenchymal Aβ plaques by 11-13 months with some vascular amyloid. Oxidative lipid damage, astrogliosis and microgliosis. No tangles. Impaired spatial learning, working memory, and contextual fear conditioning reported at <6 months although other studies have reported normal cognition at this age with progressive impairment by >12 months. Between 7 -12 weeks males become aggressive and begin to fight. Premature mortality: mortality of >20% anticipated, particularly in males. Taconic Stock #1349 and Charles River Tg2576 Hsiao et al., 1996 Yes
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 KM670/671NL (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-Aβ(4-42) C57BL6 APP Transgenic encodes N-truncated human Aβ (Aβ4-42) fused to the murine thyrotropin releasing hormone signal peptide under the control of the Thy1 promoter. APP: Transgenic Alzheimer's Disease Aβ4-42 is dectable starting at two months, predominantly in the CA1 region of the hippocampus, but also in the occipital cortex, piriform cortex, striatum, and superior colliculus. Age- and dose-dependent hippocampal neuronal loss is seen in the CA1 region as well as microgliosis and astrogliosis. Age-dependent spatial learning deficit as demonstrated in the Morris water maze, specifically, the absence of a preference for the target quadrant starting at eight months in homozygous mice and at 12 months in hemizygous mice. Impaired contextual fear conditioning. Intact vision and motor abilities. Available through Thomas Bayer. Bouter et al., 2013 Yes
B6CBA-Tg(Thy1.2-hAPParc) C57BL/6-CBA APP APP E693G (Arctic) Transgenic mice with human APP (isoform 695) bearing the Arctic APP mutation (E693G). APP: Transgenic Alzheimer's Disease Mild amyloid pathology with a relatively late onset, starting with intracellular Aβ, then diffuse extracellular Aβ deposits in the subiculum, expanding to interconnected brain regions such as retrosplenial granular cortex, thalamus, and mammillary bodies. Pathology more severe in females. Spatial learning and memory deficit in the Barnes maze test in heterozygous females mice at 15 months. Available through Annica Rönnbäck. Rönnbäck et al., 2011 No
R1 line of ES cells APP APP KM670/671NL (Swedish) Modification of mouse APP sequence to introduce the Swedish mutation and "humanize" the murine Aβ sequence by altering three amino acids. APP: Knock-In Alzheimer's Disease Accumulation of human Aβ. Unknown. Unknown. Reaume et al., 1996 No
tg ArcSwe, APP-ArcSwe C57BL/6J APP APP KM670/671NL (Swedish), APP E693G (Arctic) Transgenic mice containing human APP (isoform 695) containing both the Arctic (E693G) and Swedish (KM670/671NL) mutations under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus. Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months. Tg-ArcSwe have reduced body weight compared with nontransgenic littermates. Available through Lars Nilsson. Lord et al., 2006 Yes
APP(swe/ind) CRND8 Hybrid C3H/He-C57BL/6 APP APP KM670/671NL (Swedish), APP V717F (Indiana) Transgene contains human APP695 with the Swedish mutation (KM670/671/NL) and Indiana mutation (V717F) under the control of the hamster prion (PrP) gene promoter. The expression cassette includes about 90 nucleotides of the APP 5'-untranslated region adjacent to the start codon and 269 nucleotides of the 3′-untranslated region. APP: Transgenic Alzheimer's Disease Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months . Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests. Cholinergic dysfunction: decrease in the number of cholinergic neurons in the nucleus basalis magnocellularis by 7 months as measured by ChAT immunoreactivity. Enhanced auditory startle response and modest reduction in prepulse inhibition. Available through the Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto. Chishti et al., 2001 Yes
BRI2(Tg-FDD) Hybrid C3HeB/FeJ embryo; crossed to C57BL/6J BRI2 BRI2: Familial Danish Dementia (FDD) duplication The transgene, driven by the mouse prion promoter (Prnp), consists of the 795 form of human BRI(2) with a 10-nucleotide duplication-insertion (TTTAATTTGT). BRI2: Transgenic Familial Danish Dementia, Cerebral Amyloid Angiopathy, Alzheimer's Disease Widespread cerebral amyloid angiopathy (CAA) starting around 7 months. Deposition of the Danish amyloid subunit (ADan) in brain parenchyma and vessels, along with amyloid-associated gliosis and inflammation, intracellular and extracellular deposition of oligomeric ADan, and tau-positive deposits in neuropil, but no neurofibrillary tangles. Age-dependent abnormal grooming behavior. Around one year mice develop an arched back and walk with a wide-based gait and short steps. Feet clasping upon suspension of the mice by their tails. Available through Ruben Vidal. Vidal et al., 2009 No
mAPP/DN-RAGE, APP/DN-RAGE C57BL/6 APP, RAGE APP KM670/671NL (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: 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
APP/RAGE C57BL/6 APP, RAGE APP KM670/671NL (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: 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
APP-Swedish,Dutch,Iowa, APPSwDI C57BL/6-Tg(Thy1-APPSwDutIowa)BWevn/Mmjax C57BL/6 APP APP KM670/671NL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) Transgenic mice with 2.1 kb of the human APP gene (isoform 770) with the Swedish (K670N/M671L), Dutch (E693Q) and Iowa (D694N) mutations under the control of the mouse Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months. Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination. The Jackson Lab; available through the JAX MMRRC Stock# 034843; Live Davis et al., 2004 Yes
tg-APPSwe C57BL/6J APP APP KM670/671NL (Swedish) Transgene with human APP (isoform 695) bearing the Swedish mutation under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease Extracellular amyloid deposition begins at ~12 months. Intraneuronal Aβ aggregates at ~6 months. Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1.0% (at 12 months) and 2.8% (at 18 months). Unknown. Available through Lars Nilsson. Philipson et al., 2009, Lord et al., 2006 Yes
Tau22 C57BL6/CBA; backcrossed to C57BL6 MAPT MAPT G272V, MAPT P301S Transgene containing the cDNA of the 412 amino acid isoform of human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2 promotor. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis. Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity. Fertile with normal frequency and size of litters. Stably transmits the transgene to offspring. Deficits in hippocampal synaptic transmission. Available through Luc Buée. Schindowski et al., 2006 Yes
Thy-1 mutated human tau, TAU 441, hTAU441, TAU441 V337M R406W C57Bl/6xDBA MAPT MAPT V337M (Seattle Family A), MAPT R406W Transgene consists of human MAPT Tau441 (2N/4R) with mutations V337M and R406W under control of the Thy1 promoter. MAPT: Transgenic Alzheimer's Disease Increased total tau, and phosphorylated tau (Thr181, Ser199, Thr231) in amygdala and hippocampus starting at 3 months. Spatial memory deficits starting at 5 months (Morris water maze). Olfactory deficits at 5 months (Buried food test). No motor deficits (rota rod, beam walk) or depressive behavior (forced swim test). Olfactory deficits. QPS-Austria Flunkert et al., 2013 Yes
Segmentally trisomic Ts(1716)65Dn, Down Syndrome-segmental trisomy 16 B6EiC3Sn a/A-Ts(1716)65Dn/J DBA/2J Cesium irradiation produced a reciprocal translocation of chromosomes 16 and 17, creating a freely segregating, supernumerary chromosome Mmu1716 (1716). Other Alzheimer's Disease, Down's Syndrome Brain is grossly normal. Age-dependent cholinergic neurodegeneration and reduced NGF in the basal forebrain. Age-related elevation of APP and Aβ in the hippocampus but no β-amyloid pathology. Early developmental delay. Deficits in behavioral and cognitive tasks including spatial learning and memory deficits as assessed by the Morris water maze and the radial arm maze. Developmental delay in sensorimotor milestones. Locomotor hyperactivity. Lack of behavioral inhibition. Stereotypic behavior. Females are smaller, and produce fewer, smaller litters. Males are effectively sterile with hypospermia. The Jackson Lab: Stock# 001924; Live Davisson et al., 1990 No

48 Visualizations

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: 1mo, 3mo, 6mo, 9mo, 1yr, 15mo, 18mo+.

3xTg

Observed
  1. Plaques at 26

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

  2. Tangles at 52

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

  3. Gliosis at 30

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

  4. Changes in LTP/LTD at 26

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

  5. Cognitive Impairment at 17

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

Absent
Unknown
  • Neuronal Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN1, MAPT APP KM670/671NL (Swedish), MAPT P301L, PSEN1 M146V APP: Transgenic; PSEN1: 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.

5xFAD

Observed
  1. Plaques at 7

    Amyloid deposition begins at 1.5 months and reaches high levels especially in subiculum and deep cortical layers. Aβ42 also accumulates intraneuronally in an aggregated form within the soma and neurites starting at 1.5 months (Oakley et al., 2006).

  2. Neuronal Loss at 39

    Neuron loss in cortical layer 5 and subiculum.

  3. Gliosis at 9

    Gliosis begins at 2 months (Oakley et al., 2006).

  4. Synaptic Loss at 39

    Synaptic markers synaptophysin, syntaxin, and PSD-95 decrease with age and are significantly reduced by 9 and 12 months.

  5. Changes in LTP/LTD at 26

    LTP is normal in young animals, but becomes impaired around 6 months (Kimura et al., 2009); specifically, in hippocampal slices from < 4-month-old mice, I/O curves of fEPSPs were not different from those of wild-type controls, but the I/O responses at Schaffer collateral-CA1 synapses at 6 months were impaired.

  6. Cognitive Impairment at 17

    Impaired spatial memory in Y-maze test at 4-5 months. Impaired stress-related memory, specifically significantly lower levels of contextual freezing at 6 months. Impaired remote memory stabilization at < 4 months.

Absent
  • Tangles at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN1 APP KM670/671NL (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 and reduced anxiety.

ADanPP

Observed
  1. Plaques at 9

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

  2. Gliosis at 17

    Astrogliosis and microgliosis increase with age and increasing ADan-amyloid deposition.

  3. Cognitive Impairment at 78

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

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

Unknown
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
BRI2 BRI2: Familial Danish Dementia (FDD) duplication BRI2: Transgenic Familial Danish Dementia, Alzheimer's Disease, Cerebral Amyloid Angiopathy

ADan deposition starts in the hippocampus and meningeal vessels at 2 months and increases with age. By 18 months, deposition is widespread. The majority of amyloid deposits are associated with the vasculature, where they destroy the integrity of the vessel wall and lead to microhemorrhages. Parenchymal amyloid plaques surrounded by microglia and dystrophic neurites are also present.

Impaired performance in Morris water maze, due to a combination of both motor deficits (i.e. reduced swim speed) and spatial learning deficits reported at 18-20 months. Open field test at 18-20 months also showed an anxiety-related phenotype.

APP23

Observed
  1. Plaques at 26

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

  2. Neuronal Loss at 61

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

  3. Gliosis at 26

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

  4. Cognitive Impairment at 13

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

Absent
  • Tangles at

    Dystrophic neurites containing hyperphopshorylated tau surounds Aβ plaques, but no neurofibrillary tangles are observed (Sturchler-Pierrat et al., 1997).

  • Synaptic Loss at

    Neocortical synapses were examined in mice as old as 24 months of age; no evidence of alterations in the number of synapses or levels of synaptophysin were observed (Boncristiano et al., 2005).

  • Changes in LTP/LTD at

    LTP in the hippocampus and prefrontal cortex is normal at all ages studied: 3, 6, 9, 12, 18 and 24 months (Roder at al., 2003).

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages.

Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages.

APP751SL/PS1 KI

Observed
  1. Plaques at 11

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

  2. Neuronal Loss at 23

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

  3. Gliosis at 11

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

  4. Synaptic Loss at 24

    At 6 months, levels of pre- and post-synaptic markers are reduced (Breyhan et al., 2009).

  5. Changes in LTP/LTD at 28

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

  6. Cognitive Impairment at 27

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

Absent
  • Tangles at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN1 APP KM670/671NL (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 thioflavine-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.

APPDutch

Observed
  1. Gliosis at 126

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

Absent
  • Plaques at

    No plaques are observed, but CAA develops at 22-24 months.

  • Tangles at

    Absent.

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP E693Q (Dutch) APP: Transgenic Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type, Cerebral Amyloid Angiopathy, Alzheimer's Disease

Increased Aβ40/42 ratio. Extensive vascular Aβ deposition starting at 22-24 months appearing first in leptomeningeal vessels followed by cortical vessels, leading to smooth muscle cell degeneration, hemorrhages, and neuroinflammation. Parenchymal amyloid plaques are not observed. 

Unknown.

APP NL-F

Observed
  1. Plaques at 26

    Homozygotes develop amyloid plaques starting at 6 months in the cortex and hippocampus. Heterozygotes develop amyloidosis after 24 months. Plaques contained Aβ1-42 and pyroglutamate Aβ (Aβ3(pE)-42); Aβx-40 was a minor species.

  2. Gliosis at 26

    Microglia and activated astrocytes accumulate with age, starting around 6 months of age, concurrent with plaque formation.

  3. Synaptic Loss at 39

    Reduced synaptophysin and PSD95 immunoreactivities associated with Aβ plaques at 9-12 months.

  4. Cognitive Impairment at 78

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

Absent
  • Tangles at

    Absent; although elevated levels of phosphorylated tau are observed in dystrophic neurites around plaques.

  • Neuronal Loss at

    Absent.

Unknown
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP I716F APP: Knock-In Alzheimer's Disease

Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.

Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze.

APP NL-G-F

Observed
  1. Plaques at 9

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

  2. Gliosis at 9

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

  3. Synaptic Loss at 17

    Reduction of synaptophysin and PSD95 immunoreactivities associated with Aβ plaques in both cortical and hippocampal areas.

  4. Cognitive Impairment at 26

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

Absent
  • Tangles at

    Absent; although phosphorylated tau is elevated in dystrophic neurites around plaques.

  • Neuronal Loss at

    Absent.

Unknown
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP I716F, APP E693G (Arctic) APP: Knock-In Alzheimer's Disease

Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration.

Memory impairment by 6 months as measured by the Y maze.

APPPS1

Observed
  1. 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).

  2. 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).

  3. 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).

  4. 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).

  5. 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).

  6. 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
  • Tangles at

    Phosphorylated tau-positive neuritic processes around plaques have been observed, but no mature tangles (Radde et al., 2006).

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN1 APP KM670/671NL (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.

APPsw/0; Pdgfrβ+/-

Observed
  1. Plaques at 39

    By 9 months of age APPsw/0;Pdgfrβ+/- mice have an elevated plaque load in the cortex and hippocampus compared with age matched APPsw/0;Pdgfrβ+/+. littermates. They also have extensive cerebral amyloid angiopathy.

  2. Neuronal Loss at 39

    Progressive neuronal degeneration including reduced neurite density and reduced neuronal number in the cortex and hippocampus of APPsw/0; Pdgfrβ+/- mice at at nine months compared to age-matched APPsw/0; Pdgfrβ+/+ littermates.

  3. Cognitive Impairment at 41

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

Absent
Unknown
  • Tangles at

    Although mature neurofibrillary tangles were not observed by 9 months (the oldest age assessed), the mice develop significant tau pathology, including tau hyperphosphorylation in cortical and hippocampal neurons. Pre-tangle pathology is observed, including neuronal caspase-cleaved tau, and conformational changes as indicated by the conformation-specific antibody MC1.

  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PDGFRB APP KM670/671NL (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.

APPSwDI/NOS2-/-

Observed
  1. 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).

  2. 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).

  3. 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).

  4. 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
Unknown
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, NOS2 APP KM670/671NL (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.

APP(Swedish) (R1.40)

Observed
  1. Plaques at 59

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

  2. Gliosis at 61

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

Absent
  • Tangles at

    No mature tangles, but some changes in phosphorylated tau.

  • Changes in LTP/LTD at

    Absent.

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish) APP: Transgenic Alzheimer's Disease

By 14-16 months, homozygotes have diffuse and compact Aβ deposits in the frontal cortex, by 18-20 months plaques throughout the cortex and olfactory bulb with occasional deposits in the corpus callosum and hippocampus. No tangles, but some changes in phosphorylated tau. Reactive astrocytes and microglia by 14-16 months.

Unknown.

APPSwe/PSEN1(A246E)

Observed
  1. Plaques at 39

    Elevated Aβ42(43) peptide in the brain. By 9 months develop amyloid deposits in the cortex and hippocampus which become more numerous by 10-12 months (Borchelt et al., 1997). Aβ42 and Aβ40 codeposit (Jankowsky et al., 2004).

  2. Gliosis at 52

    Reactive gliosis in the cortex and hippocampus associated with dystrophic neurites (Borchelt et al., 1997).

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    No difference in neuronal numbers in the cingulate cortex compared with wild-type animals (Xiang et al., 2002).

Unknown
  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 A246E APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Elevated Aβ42(43) peptide in the brain. By 9 months develop amyloid deposits in the cortex and hippocampus which become more numerous by 10-12 months. Dystrophic neurites associated with gliosis in the cortex and hippocampus. Aβ42 and Aβ40 codeposit.

Poor nest building. Reduced retention on learned passive avoidance task. Increased immobility time in forced swim task.

APPswe/PSEN1dE9

Observed
  1. 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).

  2. 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).

  3. 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).

  4. 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
  • Tangles at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN1 APP KM670/671NL (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.

Impairment in the Morris water maze at 12 months. High incidence of seizures.

APP(V642I)KI

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

    Absent.

  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP V717I (London) APP: Transgenic Alzheimer's Disease

Increased Aβ42(43) relative to Aβ40 at 29 months, but without neuritic plaques, neurofibrillary tangles, massive neuronal loss, or brain atrophy.

At 27-29 months mice displayed long-term memory deterioration. Acquisition of spatial memory is slightly affected, but no deterioration in short-term working memory. No difference in open field test or elevated plus maze suggesting no difference in overall behavioral patterns or activity levels.

APP(V717I)

Observed
  1. Plaques at 43

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

  2. Gliosis at 43

    GFAP, microglial activation, and other markers of brain inflammation are elevated by 10 months.

  3. Changes in LTP/LTD at 26

    Significant deficit in LTP in CA1 region of the hippocampus at 6 months.

  4. Cognitive Impairment at 26

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

Absent
  • Tangles at

    Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.

  • Neuronal Loss at

    Absent.

Unknown
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP V717I (London) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Plaques start in the subiculum, spreading to the frontal cortex as dense and diffuse aggregates. Prominent amyloid deposits in brain vessels after 15 months. Microbleeds. Amyloid-associated inflammation. CSF Aβ42/Aβ40 ratio decreases from 15 months. Dystrophic neurites containing hyperphosphorylated tau, but no tangle pathology.

From the age of 6 months, spatial and non-spatial orientation and memory deficits by Morris water maze. Impaired associative learning. Increased agitation/anxiety from 8 weeks. Reduced ambulation, especially with age. Hyperactivity and aggression.

APP(V717I) x PS1(A246E)

Observed
  1. Plaques at 17

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

  2. Gliosis at 20

    Elevated GFAP, microglial activation, and other markers of brain inflammation increase as of 4.5 months.

  3. Changes in LTP/LTD at 26

    Significant deficit in LTP in CA1 region of the hippocampus at 6 months.

  4. 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
  • Tangles at

    Dystrophic neurites containing hyperphosphorylated murine tau, but no tangle pathology.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
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.

Arc48 (APPSw/Ind/Arc)

Observed
  1. Plaques at 9

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

  2. Gliosis at 13

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

  3. Cognitive Impairment at 13

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

Absent
  • Tangles at

    Absent.

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP V717F (Indiana), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Parenchymal neuritic plaques by 2 months accompanied by dystrophic neurites. Prominent hippocampal Aβ deposition by 3-4 months. Relatively low Aβ42/Aβ40 ratio. Comparable cerebrovascular amyloid deposition to J20.

At 3-4 months the Arc48 mouse was able to learn a task involving escape to a cued platform in the Morris water maze, but had an impaired ability to use extramaze cues to navigate to the hidden platform.

ArcAβ

Observed
  1. Plaques at 39

    Between 9 and 15 months of age β-amyloid plaques became prominent. Plaques had a characteristic dense core morphology which differed from the cotton wool-like structure of plaques seen with the Swedish mutation alone.

  2. Cognitive Impairment at 26
    Cognitive impairment measured from the age of 6 months in the Morris water maze and Y-maze as well as in active avoidance behavior.
Absent
  • Tangles at

    Absent.

Unknown
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease At 6 months intracellular punctate deposits of Aβ abundant in cortex and hippocampus, but overt β-amyloid plaques not apparent until 9-15 months. Severe CAA also present at this age with dense Aβ aggregates in blood vessels walls and spreading into the parenchyma.

Cognitive impairments from the age of 6 months measured in the Morris water maze and Y-maze.

BRI-Aβ42 (BRI2-Aβ42)

Observed
  1. Plaques at 13

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

  2. Gliosis at 13

    Plaque-associated reactive gliosis as measured by GFAP immunostaining.

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

  • Cognitive Impairment at

    On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Detergent-insoluble amyloid-β appearing with age and cored plaques as early as 3 months in the cerebellum. Variable forebrain pathology later with extracellular Aβ plaques in the hippocampus and entorhinal/piriform cortices at 12 months. Age-associated congophillic amyloid angiopathy. No tangles or neuronal loss.

On a mixed (C57/B6//C3H) background hemizygous mice have intact cognition as measured by fear conditioning at 12 months and 14-17 months despite accumulating amyloid.

htau

Observed
  1. Tangles at 39

    Aggregated tau and paired helical filaments detectable at 9 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 6 months, and increases further by 13 and 15 months (Andorfer et al., 2003).

  2. 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 8 months to 18 months. Decrease in the thickness of the corpus callosum (Andorfer et al., 2005).

  3. Changes in LTP/LTD at 52

    In hippocampal slices, LTP induced by high frequency stimulation (HFS) was normal at 4 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 4 months, but increased at 12 months compared to controls, suggesting a decrease in probability of transmitter release (Polydoro et al., 2009).

  4. Cognitive Impairment at 26

    Abnormal spatial learning in 6 month-old mice compared to control mice (Phillips et al., 2011). Normal object recognition and spatial learning and memory by MWM at 4 months, but deficits by 12 months (Polydoro et al., 2009).

Absent
Unknown
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
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 4 months, but were impaired at 12 months (Polydoro et al., 2009).

hTau.P301S

Observed
  1. Tangles at 17

    Neurofibrillary tangles detected as early as 4 months of age.

  2. Neuronal Loss at 13

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

  3. Gliosis at 22

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

Absent
  • Plaques at

    Absent.

Unknown
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT P301S MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tangle like pathology in the cerebral cortex, hippocampus, brain stem and the spinal cord. Neurodegeneration, especially in the spinal cord, which is accompanied by astrocytosis.

Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2-3 months.

J20 (PDGF-APPSw,Ind)

Observed
  1. Plaques at 22

    At 5-7 months of age diffuse amyloid-β plaques deposit in the dentate gyrus and neocortex. Amyloid deposition is progressive with widespread plaques by 8-10 months.

  2. Neuronal Loss at 12

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

  3. Gliosis at 24

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

  4. Synaptic Loss at 35

    Age-dependent loss of synaptophysin immunoreactivity in presynaptic terminals is observed by 8-10 months, but does not correlate with plaque load (Mucke et al., 2000).

  5. Changes in LTP/LTD at 13

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

  6. Cognitive Impairment at 16

    Deficits in spatial memory and learning appear as the mice age. As early as 16 weeks mice demonstrate spatial reference memory deficits as measured by the radial arm maze (Wright et al., 2013). By 6-7 months deficits appear in spatial memory retention and acquisition in the water maze (Palop et al., 2003).

Absent
  • Tangles at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

Age-dependent formation of Aβ plaques. Dystrophic neurites associated with plaques. No tangles. Variable cell loss. Decrease in synaptophysin immunoreactvity.

Learning and memory deficits are age-dependent and may appear as early as 16 weeks. Hyperactivity and increased time in the open arm of the elevated plus maze than wild-type mice indicating lower levels of anxiety, but has not been universally replicated.

JNPL3(P301L)

Observed
  1. Tangles at 20

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

  2. Neuronal Loss at 43

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

  3. Gliosis at 43

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

Absent
  • Plaques at

    Absent.

Unknown
  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT P301L MAPT: Transgenic Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease

Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord.

By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization.

mThy1-hAPP751 (Line 41)

Observed
  1. Plaques at 13

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

  2. Gliosis at 27

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

  3. Synaptic Loss at 52

    Dystrophic neurites and synaptic loss starting at 12 months.

  4. Cognitive Impairment at 26

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

Absent
  • Tangles at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP V717I (London) APP: Transgenic Alzheimer's Disease

Age-dependent increases in Aβ40 and Aβ42, with Aβ42 > Aβ40. Plaques at an early age, starting at 3-6 months in the frontal cortex. At 5-7 months, size and number of plaques increased in the frontal cortex, and dense amyloid deposits appear in hippocampous, thalamus, and olfactory region.

Age-associated impairment in spatial memory and learning in the water maze task and habituation in the hole-board task, with significant deficits at 6 months of age. Some gender-specific differences in open field exploration.

PDAPP(line109)

Observed
  1. Plaques at 26

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

  2. Gliosis at 26

    GFAP-positive astrocytes and activated microglia associated with plaques (Games et al., 1995).

  3. Synaptic Loss at 35

    Decreased synaptic density in the dentate gyrus as measured by synaptophysin immunoreactivity. Also decreased dendritic density as measured by MAP2 immunoreactivity (Games et al., 1995).

  4. Changes in LTP/LTD at 17

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

  5. Cognitive Impairment at 13

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

Absent
  • Tangles at

    No paired helical filaments or aggregates, but phosphorylated tau immunoreactivity is observed in dystrophic neurites after 14 months (Masliah et al., 2001).

  • Neuronal Loss at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

Amyloid plaques in the hippocampus, cerebral cortex. Gliosis. Dystrophic neurites. Decreased synaptic and dendritic density in the hippocampus.

Deficits in a variety of memory paradigms from a young age. Deficits in the radial arm maze at 3 months (before plaques), object recognition, operant learning, spatial reference memory (starting at 3-4 months), cued fear conditioning at 11 months.

PLB4 (hBACE1)

Observed
  1. Gliosis at 52

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

  2. Cognitive Impairment at 13

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

Absent
  • Plaques at

    Plaques virtually absent, minimal small sparse plaques. However, prominent extracellular Aβ staining surrounding neuronal cell bodies, including Aβ multimers (e.g. Aβ*56 and Aβ hexamers).

  • Tangles at

    Preliminary analysis did not find abnormal phosphorylation or conformational changes in tau.

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
BACE1 BACE1: Transgenic Alzheimer's Disease

Elevated extracellular multimeric Aβ, including Aβ*56 and Aβ hexamers, in the absence of plaques. At 12 months of age, astrogliosis was observed in a region- and genotype-dependent manner, especially in the dentate gyrus, hippocampal CA1, and piriform cortex. No overt tau pathology.

Largely intact motor coordination and gait (Rotarod, CatWalk). Age-associated changes in multiple measures of learning and memory. Early deficits in habituation to a novel environment and semantic-like memory (three-four months). Impaired spatial learning and long-term reference (Morris water maze) and working memory (Y-maze) at six months, distinct from reduced locomotor activity and anxiety.

PS1 cKO

Observed
  1. Cognitive Impairment at 22

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

Absent
  • Plaques at

    Absent.

  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

  • Changes in LTP/LTD at

    Mice at 3-6 months of age exhibit normal paired-pulse facilitation, LTP, and LTD in the Schaffer collateral pathway of the hippocampus (Yu et al., 2001).

Unknown
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
PSEN1 PSEN1: Conditional Knock-out Alzheimer's Disease

Reduction in Aβ40 and Aβ42 peptides; accumulation of APP C-terminal fragments.

Subtle but significant deficits in long-term spatial memory in the Morris water maze.

PS2APP

Observed
  1. 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).

  2. Gliosis at 26

    Gliosis at 6 months (personal communication, Laurence Ozmen).

  3. 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).

  4. 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
  • Tangles at

    Absent.

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN2 APP KM670/671NL (Swedish), PSEN2 N141I (Volga German) 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.

PS2APP (PS2(N141I) x APPswe)

Observed
  1. 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).

  2. 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.

  3. 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
  • Tangles at

    Absent.

  • Changes in LTP/LTD at

    No difference in LTP in the dentate gyrus at 3 and 10 months compared to wild-type mice (Richards et al., 2003).

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN2 APP KM670/671NL (Swedish), PSEN2 N141I (Volga German) 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.

PS/APP

Observed
  1. 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).

  2. 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).

  3. 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).

  4. 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
  • Tangles at

    Neurofibrillary tangles are not associated with this model, but hyperphosphorylated tau is detected, starting at 24 weeks, appearing as punctate deposits near amyloid deposits in the cortex and hippocampus (Kurt et al., 2003).

Unknown
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, PSEN1 APP KM670/671NL (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.

PS cDKO

Observed
  1. 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.

  2. 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). 

  3. 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).

  4. 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
  • Plaques at

    Absent.

  • Tangles at

    Tangles are absent, but hyperphosphorylation of tau has been reported in 9 month-old mice.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
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.

rTg(tauP301L)4510

Observed
  1. Tangles at 17

    Pretangles as early as 2.5 months. Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months (SantaCruz et al., 2005).

  2. Neuronal Loss at 24

    Decreased (~60%) CA1 hippocampal neurons by 5.5 months with significant loss in brain weight. Progressive loss of neurons and brain weight in 7 and 8.5 month mice with ~23% of CA1 pyramidal cells remaining at 8.5 months. Gross atrophy of the forebrain by 10 months (SantaCruz et al., 2005).

  3. Synaptic Loss at 35

    Significant loss of dendritic spines at 8-9 months (~30% decrease in spine density in somatosensory cortex)(Kopeikina et al., 2013).

  4. Cognitive Impairment at 11

    No significant abnormalities at 1.3 months but the retention of spatial memory examined by Morris Water Maze became impaired from 2.5 to 4 months. No significant motor impairments up to 6 months. Spatial memory improved when transgene suppressed by dox (SantaCruz et al., 2005).

Absent
  • Plaques at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT P301L MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60%) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (6 to 8 weeks) suppression of transgenic tau.

No significant abnormalities at 1.3 months in the Morris Water Maze. Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months. When the transgene was suppressed with dox at 2.5 months spatial memory improved.

Tau P301L

Observed
  1. Tangles at 35

    Hyperphosphylation, conformational changes, and aggregation of tau resulting in tangle-like pathology by 8 months.

  2. Gliosis at 30

    Astrogliosis by 7 months.

  3. Changes in LTP/LTD at 26

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

  4. Cognitive Impairment at 22

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

Absent
  • Plaques at

    Absent.

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown at advanced age. Young mice (1-2 months) have a significantly higher spine maturation index than controls. At 4-6 months, the spine maturation index remains high in the hippocampus, but is reduced to control levels in the cortex. Note, these results were generated using the progeny of Tau P301L x transgenic Thy1-YFP (Kremer et al., 2011).

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT P301L MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF.

Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months.

Tau P301S (Line PS19)

Observed
  1. Tangles at 23

    Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem and spinal cord at 6 months with progressive accumulation (Yoshiyama et al., 2007).

  2. Neuronal Loss at 39

    Neuron loss in the hippocampus and entorhinal cortex by 9-12 months, as well as in the amygdala and neocortex becoming more severe by 12 months (Yoshiyama et al., 2007).

  3. Gliosis at 11

    Microgliosis at 3 months, especially in the white matter of the brain and spinal cord. Increased microgliosis by 6 months in white and gray matter of the hippocampus, amygdala, entorhinal cortex and spinal cord. Microglial activation precedes astrogliosis (Yoshiyama et al., 2007).

  4. Synaptic Loss at 13

    Synaptophysin immunoreactivity decreased progressively from 3-6 months in the CA3 region of the hippocamus. Impaired synaptic function (Yoshiyama et al., 2007).

  5. Changes in LTP/LTD at 26

    Reduced LTP in the CA1 region of the hippocampus at 6 months. Altered basal synaptic transmission (smaller fiber volley amplitude, fEPSP slopes, and amplitudes) (Yoshiyama et al., 2007).

  6. Cognitive Impairment at 27

    Impairments in spatial learning and memory ability in the Morris water maze in 6 month old animals (Takeuchi et al., 2011).

Absent
  • Plaques at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT P301S MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis.

Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months.

TauPS2APP

Observed
  1. 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).

  2. 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).

  3. 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
  • Neuronal Loss at

    No overt neuronal loss in the hippocampus at 16 months (Grueninger et al., 2010).

Unknown
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, MAPT, PSEN2 APP KM670/671NL (Swedish), MAPT P301L, PSEN2 N141I (Volga German) 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.

TAU R406W

Observed
  1. Tangles at 78

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

  2. Cognitive Impairment at 70

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

Absent
  • Plaques at

    Absent.

Unknown
  • Neuronal Loss at

    Unknown.

  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT R406W MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

Argyrophilic and congophilic tau inclusions in neurons of the forebrain with age. Detectable with Congo red, thioflavin-S and Gallyas silver stain. Congophilic tau inclusions also in the hippocampus and amygdala. Mainly straight tau filaments.

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

Tau V337M

Observed
  1. Tangles at 48

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

  2. Neuronal Loss at 43

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

  3. Changes in LTP/LTD at 65

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

  4. Cognitive Impairment at 48

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

Absent
  • Plaques at

    Absent.

Unknown
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT V337M (Seattle Family A) MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

SDS-insoluble tau aggregates in hippocampus. Degenerating neurons in the hippocampus containing phosphorylated and ubiquitinated tau aggregates with β-sheet structure.

Higher overall spontaneous locomotion than non-transgenic littermates in elevated plus maze. No differences in the Morris water maze.

TBA42

Observed
  1. Plaques at 52

    Very rare extracellular Aβ deposits at all ages tested.

  2. Gliosis at 52

    Marked gliosis in the hippocampus as measured by GFAP staining at 12 months.

  3. Cognitive Impairment at 54

    Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at 3 and 6 months.

Absent
  • Tangles at

    Absent.

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP: Transgenic Alzheimer's Disease

Intraneuronal accumulation of Aβ peptides in the hippocampus by three months and in cerebellar nuclei by six months. Marked gliosis in the hippocampus by 12 months. Very rare extracellular Aβ deposits.

Age-dependent behavioral deficits, including working memory as assessed by the cross maze at 12 months, but not at three and six months. Early and persistent decrease in anxiety in the elevated plus maze. Comparable to wild-type in general motor coordination at three and six months as indicated by the balance-beam test, but impairment at 12 months.

Tg2576

Observed
  1. Plaques at 48

    Numerous parenchymal Aβ plaques by 11-13 months.

  2. Gliosis at 43

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

  3. Synaptic Loss at 20

    Dendritic spine loss by 4.5 months In the CA1 region of the hippocampus (Lanz et al., 2003).

  4. Changes in LTP/LTD at 22

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

  5. Cognitive Impairment at 26

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

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent or very limited.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish) APP: Transgenic Alzheimer's Disease

Numerous parenchymal Aβ plaques by 11-13 months with some vascular amyloid. Oxidative lipid damage, astrogliosis and microgliosis. No tangles.

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

Tg2576/Tau(P301L) (APPSwe-Tau)

Observed
  1. 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.

  2. 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).

  3. 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
Unknown
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP, MAPT APP KM670/671NL (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.

Tg4-42

Observed
  1. Neuronal Loss at 35

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

  2. Gliosis at 9

    Reactive microglia and astrocytes in the hippocampus starting at 2 months.

  3. Synaptic Loss at 37

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

  4. Cognitive Impairment at 35

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

Absent
  • Plaques at

    Absent.

  • Tangles at

    Absent.

Unknown
  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP: Transgenic Alzheimer's Disease

Aβ4-42 is dectable starting at two months, predominantly in the CA1 region of the hippocampus, but also in the occipital cortex, piriform cortex, striatum, and superior colliculus. Age- and dose-dependent hippocampal neuronal loss is seen in the CA1 region as well as microgliosis and astrogliosis.

Age-dependent spatial learning deficit as demonstrated in the Morris water maze, specifically, the absence of a preference for the target quadrant starting at eight months in homozygous mice and at 12 months in hemizygous mice. Impaired contextual fear conditioning.

Tg-ArcSwe

Observed
  1. Plaques at 22

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

  2. Gliosis at 26

    Microgliosis and astrogliosis most prominent in the hippocampus, but also locally around deposits in the cerebral cortex and thalamus.

  3. Cognitive Impairment at 17

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

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

Unknown
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP E693G (Arctic) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

Strong intraneuronal Aβ aggregation starting at 1 month and increasing with age. Extracellular amyloid plaque at 5-6 months, most consistent in the cerebral cortex, hippocampus, and thalamus. Congophilic parenchymal plaques are predominant, but some mice show marked CAA, particularly in the thalamus.

Mild spatial learning deficits at 4-8 months in Morris water maze and impaired functioning in a passive avoidance test at 16 months.

TgCRND8

Observed
  1. Plaques at 13

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

  2. Neuronal Loss at 26

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

  3. Gliosis at 13

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

  4. Synaptic Loss at 26

    Reduced synaptophysin immunoreactivity in the vicinity of plaques at 6 months (Adalbert et al., 2009).

  5. Changes in LTP/LTD at 26

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

  6. Cognitive Impairment at 13

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

Absent
  • Tangles at

    Neurofibrillary tangles are absent (Chishti et al., 2001). Tau is hyperphosphorylated, nitrosylated and aggregated at 7-12 months especially in the neocortex, dentate gyrus, and the CA1 and CA3 areas of the hippocampus (Bellucci et al., 2007).

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP V717F (Indiana) APP: Transgenic Alzheimer's Disease

Rapid, early plaque development, with thioflavin S-positive amyloid deposits at 3 months; dense cored plaques and neuritic pathology by 5 months. Plaques become more extensive with age. More Aβ42 than Aβ40. Activated microglia appear concurrently with plaques, whereas GFAP+ astrocytes follow later, about 13-14 weeks. Dystrophic neurites at 5 months .

Early impairment in acquisition and learning reversal in the reference memory version of the Morris water maze by 3 months. Cognitive deficits in the step-down inhibitory avoidance test at 7 months but not at 2 months. Similar to wild-type in motility, exploratory activity, or neuromuscular function at 7 months as evaluated by the rotarod, hole board and grip strength tests.

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

Observed
  1. Plaques at 13

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

  2. Gliosis at 26

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

  3. Cognitive Impairment at 13

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

Absent
  • Tangles at

    Absent.

Unknown
  • Neuronal Loss at

    Unknown.

  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish), APP E693Q (Dutch), APP D694N (Iowa) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy, Hereditary Cerebral Hemorrhage with Amyloidosis of the Dutch type

Hemizygotes progressively accumulate insoluble Aβ40 and Aβ42, especially within brain microvessels starting at 3 months. Fibrillar Aβ in micovessels around 6 months. Diffuse plaque-like deposits around 3 months in the subiculum, hippocampus and cortex. Aβ deposits throughout the forebrain by 12 months.

Impaired learning and memory in the Barnes maze task at 3, 9, and 12 months. Beginning at 3 months transgenic mice took longer to find the escape hole. No difference in mobility, strength or coordination.

Tg-Swe

Observed
  1. Plaques at 52

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

  2. Gliosis at 52

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

Absent
  • Tangles at

    Absent.

  • Neuronal Loss at

    Absent.

Unknown
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
APP APP KM670/671NL (Swedish) APP: Transgenic Alzheimer's Disease

Extracellular amyloid deposition begins at ~12 months. Intraneuronal Aβ aggregates at ~6 months. Extracellular pathology, both cerebrovascular amyloid angiopathy (CAA) and congophilic parenchymal plaques, mainly found in the cerebral cortex, hippocampus and thalamus. Aβ-burden in cerebral cortex is approximately 1.0% (at 12 months) and 2.8% (at 18 months).

Unknown.

THY-Tau22

Observed
  1. Tangles at 13

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

  2. Neuronal Loss at 52

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

  3. Gliosis at 13

    Age-dependent increase in the number of GFAP+ astrocytes in the hippocampus (hilus, CA1, CA3), cerebral cortex, corpus callosum (Schindowski et al., 2006).

  4. Changes in LTP/LTD at 39

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

  5. Cognitive Impairment at 26

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

Absent
  • Plaques at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT G272V, MAPT P301S MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis.

Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity.

TMHT (Thy-1 mutated human tau)

Observed
  1. Tangles at 17

    Tangles at 4 months and progress with age.

  2. Cognitive Impairment at 22

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

Absent
  • Plaques at

    Absent.

Unknown
Genes Mutations Modification Disease Neuropathological
Phenotype
Neurological/Behavioral
Phenotype
MAPT MAPT V337M (Seattle Family A), MAPT R406W MAPT: Transgenic Alzheimer's Disease

Increased total tau, and phosphorylated tau (Thr181, Ser199, Thr231) in amygdala and hippocampus starting at 3 months.

Spatial memory deficits starting at 5 months (Morris water maze). Olfactory deficits at 5 months (Buried food test). No motor deficits (rota rod, beam walk) or depressive behavior (forced swim test).