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23 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathology Behavior/Cognition Other Phenotype Availability Primary Paper Visualization
Mouse Models (22)
<p>-</p>, <p>3xTg-AD</p>, <p>The LaFerla mouse</p> B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/Mmjax C7BL/6;129X1/SvJ;129S1/Sv Psen1, APP, MAPT APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V Single-cell embryos from mice with knock-in of PSEN1 with the PS1M146V mutation were injected with two human transgenes (APP with the Swedish mutation and MAPT with the P30IL mutation). Transgenes integrated at a single locus under the control of the mouse Thy1.2 promoter. Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic Alzheimer's Disease Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles. Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task. The Jackson Lab; available through the JAX MMRRC Stock# 034830; Live Oddo et al., 2003 Yes
<p>-</p>, <p>AAV-sTREM2 Tau P301S</p> Tau P301S (Line PS19) TREM2, MAPT MAPT P301S Adeno-associated viruses (AAV2/8) expressing EGFP- and FLAG-tagged human TREM2 (amino acids 1-171) under the control of the CAG promoter were injected bilaterally into the hippocampi of 3-month-old male PS19 mice. Control mice received injections of AAV expressing only EGFP. TREM2: Virus; MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice. AAV-mediated expression of sTREM2 improved performance of PS19 mice in the Morris water maze and Y-maze. Levels of p-tau202 and p-tau396 and activity of GSK3β were lower in AAV-sTREM2 PS19 mice compared with PS19 mice who received control vector. PS19 mice are available from The Jackson Lab: Stock# 008169; Live. Research with PS19 mice is available from Scantox Neuro. Zhang et al., 2023 Yes
<p>-</p>, <p>Tau.P301S</p>, <p>hTAU[P301S]</p>, <p>tau[P301S]</p>, <p>Tg2541</p> Thy1-hTau.P301S (CBA.C57BL/6) CBAxC57BL/6 MAPT MAPT P301S Transgenic mice overexpressing a human tau isoform that is 383 amino acids long with four microtubule-binding repeat domains and without N-terminal inserts (4R/0N). Site-directed mutagenesis was used to introduce the P301S mutation. Transgene is under the control of the neuron-specific murine Thy-1 promoter. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Age-dependent hyperphosphorylation of tau and conformational changes leading to neurofibrillary tanglelike pathology in the cerebral cortex, hippocampus, brain stem, and spinal cord. Neurodegeneration, especially in the spinal cord, accompanied by astrocytosis. Early motor impairment, including abnormal clasping and rotarod deficit at 4 months, with nearly complete deficit at 5 months. Deficits progress to severe paraparesis. Disinhibition and hyperactivity at 2 to 3 months. Muscle weakness, tremor. Frequent eye inflammation. Available for academic use from Michel Goedert and for commercial use from LifeArc. Also available from The Mary Lyon Centre at MRC Harwell, Archive# HAR: 011664. The CRO reMYND offers research services with this line. Allen et al., 2002 Yes
<p>-</p>, <p>TauP301L-JNPL3</p> Tg(Prnp-MAPT*P301L)JNPL3Hlmc C57BL/6, DBA/2, SW Mixed Background MAPT MAPT P301L Transgene for human MAPT (4R0N) with the P301L mutation driven by the mouse prion promoter. MAPT: Transgenic Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease Age and gene-dose dependent development of neurofibrillary tangles as early as 4.5 months in homozygotes and 6.5 months in heterozyotes. Tangles and Pick-body-like inclusions in the amygdala, hypothalamus, pons, medulla, and spinal cord among other areas. Neuronal loss, especially in the spinal cord. By 10 months, 90% developed motor and behavioral disturbances including limb weakness, hunched posture, decrease in grooming and vocalization. Eye irritiation, possibily due to carrying the Pde6brd1 retinal degeneration mutation carries Pde6brd1 mutation Taconic: Stock#2508 (homozygote); #1638 (heterozygote and wild-type) has been discontinued. Lewis et al., 2000 Yes
B6(Cg)-Tc(HSA17*)1Mdk/J C57BL/6J MAPT, MAPT-AS1, Mapt MAPT IVS10+16 C>T A 190-kb region from human chromosome 17—including MAPT (H1 haplotype) with the IVS10+16 C>T mutation in intron 10, MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1. MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Frontotemporal Dementia Unknown. Unknown. Unknown. Available from The Jackson Laboratory, Stock No. 036664. Benzow et al., 2024 Yes
B6J.B6N-Tc(HSA17)2Mdk/J C57BL/6J MAPT, MAPT-AS1, Mapt A 190-kb region from human chromosome 17—including MAPT (H1 haplotype), MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1. MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Unknown. Unknown. Available from The Jackson Laboratory, Stock No. 035398. Benzow et al., 2024 Yes
B6J.B6N-Tc(HSA17*N279K)1Mdk/J C57BL/6J MAPT, MAPT-AS1, Mapt MAPT N279K A 190-kb region from human chromosome 17—including MAPT (H1 haplotype) with the N279K mutation, MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1. MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Frontotemporal Dementia Unknown. Unknown. Available from The Jackson Laboratory, Stock No. 035794. Benzow et al., 2024 Yes
B6J.B6N-Tc(HSA17*P301L)1Mdk/J C57BL/6J MAPT, MAPT-AS1, Mapt MAPT P301L A 190-kb region from human chromosome 17—including MAPT (H1 haplotype) with the P301L mutation, MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1. MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Frontotemporal Dementia Unknown. No overt behavioral phenotypes Unknown. Available from The Jackson Laboratory, Stock No. 037420. Benzow et al., 2024 Yes
B6J.B6N-Tc(HSA17)1Mdk/J C57BL/6J MAPT, MAPT-AS1, Mapt A 190-kb region from human chromosome 17—including MAPT (H2 haplotype), MAPT-AS1, and the SPPL2C sequence, which is contained within MAPT-AS1—replaced a 157-kb region on mouse chromosome 11 between, but not including, Crhr1 and Kansl1. MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Unknown. Unknown. Available from The Jackson Laboratory, Stock No. 033668. Benzow et al., 2024 Yes
<p>hAPP/hTau/hPS1</p>, <p>PLB1(Triple)</p> C57BL6 APP, MAPT, PSEN1 APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W Targeted insertion of human APP and tau sequences at the HPRT site on the X chromosome, driven by mouse CaMKII-α. Human APP (isoform 770) with the Swedish and London mutations. Human tau (isoform 2N/4R, 441 amino acids) with P301L and R406W. APP/tau-expressing animals (PLB1-double) were crossed with hPS1 (A246E) transgenic mice (Borchelt et al., 1997) to generate the triple transgenic. APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene Alzheimer's Disease Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT. Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity. Litter size and overall health were normal. Mice spent more time awake at six months and had fragmented sleep. Quantitative EEG showed heightened delta power during wakefulness and REM sleep. Available through Bettina Platt Platt et al., 2011 Yes
<p>-</p>, <p>PS19-TREM2<sup>CV</sup></p>, <p>PS19-T2<sup>CV</sup></p> C57BL/6 MAPT, TREM2, Trem2 MAPT P301S These mice carry a human MAPT transgene with the P301S mutation linked to frontotemporal dementia and a BAC transgene encoding the common variant of human TREM2, on a mouse-Trem2-null background. MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia Brain atrophy by 9 months of age. Increased microgliosis, astrogliosis and synapse loss, compared with PS19 mice carrying TREM2 with the R47H mutation. Not known. Increased expression of pro-inflammatory cytokines and DAM (disease-associated microglia) genes, compared with PS19 mice carrying TREM2 with the R47H mutation. PS19 mice are available from The Jackson Laboratory (Stock# 008169). TREM2 mice are available through Marco Colonna. Gratuze et al., 2020 Yes
<p>-</p>, <p>PS19-T2<sup>R47H</sup></p>, <p>PS19-TREM2<sup>R47H</sup></p> C57BL/6 MAPT, TREM2, Trem2 MAPT P301S, TREM2 R47H These mice carry a human MAPT transgene with the P301S mutation linked to frontotemporal dementia and a BAC transgene encoding the R47H variant of human TREM2, on a Trem2 knockout background. MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2. Not known. Decreased expression of pro-inflammatory cytokines and DAM (disease-associated microglia) genes, compared with PS19 mice carrying the common variant of TREM2. PS19 mice are available from The Jackson Laboratory (Stock# 008169). TREM2 mice are available through Marco Colonna. Gratuze et al., 2020 Yes
<p>-</p>, <p>neuropsin-tTA x FVB-Tg(tetO-tauP301L)4510</p> 4510 mice are on an FVB background. Neuropsin-tTA mice are on a C57BL/6 background. MAPT MAPT P301L Bigenic mice made by crossing an activator line, neuropsin-tTA, with a responder line, Tg(tetO-tauP301L)4510. The neuropsin promoter drives the tetracycline transactivator (tTA) transgene preferentially in a subset of entorhinal neurons. tTA drives expression of human tau (4R0N) with the P301L mutation. Transgene expression in bigenic mice is constitutive until suppressed by doxycycline. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss. Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test. No apparent change in anxiety as assessed by the open field test. Reduced Arc induction in the hippocampus after contextual fear conditioning. Subtle differences in basal synaptic transmission with enhanced axonal excitability. Unknown. de Calignon et al., 2012 Yes
<p>-</p>, <p>rTg4510</p>, <p>rTg(tetO-TauP301L)4510</p>, <p>Tau P301L</p> 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ; Fgf14Tg(tetO-MAPT*P301L)4510Kha/J. Formerly: 129S6.Cg-Tg(Camk2a-tTA)1Mmay/JlwsJ; FVB-Tg(tetO-MAPT*P301L)#Kha/JlwsJ Mixed: 129S6 (activator) X FVB (responder) MAPT MAPT P301L Bi-transgenic mice are made by crossing an activator line, CaMKIIα-tTA, with a responder line, Tg(tetO-tauP301L)4510. The CaMKIIα promoter drives the tetracycline transactivator (tTA) transgene preferentially in forebrain neurons. tTA drives expression of human tau (4R0N) with the P301L mutation. Transgene expression in bi-transgenic mice is constitutive until suppressed by doxycycline. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months. Decreased CA1 neurons (~60 percent) by 5.5 months. Gross forebrain atrophy by 10 months. The number of CA1 neurons stabilized after a brief (six to eight week) suppression of transgenic tau. Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved. Homozygous mice are not viable. It should be noted that disruption of an endogenous mouse gene, caused by random insertion of the MAPT transgene, significantly contributes to the neuropathological and neurodegenerative phenotypes observed in rTg4510 mice 4510 responder line: The Jackson Lab: Stock# 015815; Activator line: The Jackson Lab: Stock# 016198. Santacruz et al., 2005, Ramsden et al., 2005, Gamache et al., 2019 Yes
<p>-</p>, <p>Tau<sup>A152T</sup>-AAV</p> C57BL/6 MAPT MAPT A152T An adeno-associated viral (AAV1) vector encoding TauA152T under the control of the cytomegalovirus enhancer/chicken β-actin promoter was injected bilaterally into the lateral ventricles of neonatal C57BL/6 mice. MAPT: Virus Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Neuron loss and astrogliosis were observed in the cortices of 3-month-old mice. Compared with GFP-AAV controls, TauA152T-AAV mice showed deficits in contextual and cued fear conditioning, increased hyperactivity, and decreased rearing in the open-field test, and spent more time in the open arms of the elevated plus maze. TauA152T-AAV mice also exhibited motor impairment on the Rotarod. Unknown. Carlomagno et al., 2019 Yes
<p>-</p>, <p>Tau.P301L</p>, <p>hTau.P301L</p>, <p>Tau-4R-P301L</p>, <p>Tau(P301L)</p> Thy1-hTau.P301L FVB/N MAPT MAPT P301L These transgenic mice overexpress the human Tau-4R/2N isoform bearing the P301L mutation under the control of the neuron-specific murine Thy1 promoter. MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Pathologic hyperphosphorylation and conformational change of parenchymal tau in brain tissues starting at 7 months. Tangle-like pathology is mainly observed in the brain stem and spinal cord, and to a lesser extent in the midbrain and cerebral cortex. Age-dependent increase in total tau in CSF. Age-associated deficits in a passive avoidance task (starting at 5 months) and a novel object recognition task (starting at 9 months). At a young age (~2 months) outperforms wild-type littermates in object recognition memory. Progressive motor impairment and reduced activity, accompanied by increased clasping of hind and then forelimbs around seven months. Premature death around 8-12 months, preceded by weight loss, hyperkyphosis, reduced activity, and upper airway dysfunction. The CRO reMYND offers research services with this line.  Terwel et al., 2005 Yes
<p>-</p>, <p>Tau<sup>P301L</sup>-AAV</p> C57BL/6 MAPT MAPT P301L An adeno-associated viral (AAV1) vector encoding TauP301L under the control of the cytomegalovirus enhancer/chicken β-actin promoter was injected bilaterally into the lateral ventricles of neonatal C57BL/6 mice. MAPT: Virus Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy Neurofibrillary tangles and gliosis, but no cortical neuron loss, at 6 months of age. Hyperactivity in the open field, decreased time spent in the center of open field, more time spent in the open arms of the elevated plus maze, and deficits in cued and contextual fear conditioning at 6 months of age. Unknown. Cook et al., 2015 Yes
<p>Line PS19</p>, <p>PS19Tg</p> B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J (C57BL/6 x C3H)F1 MAPT MAPT P301S Transgenic line expressing mutant human tau under the direction of the mouse prion protein (Prnp) promoter. The transgene codes for tau with four microtubule-binding domains and one N-terminal insert (4R/1N). MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia Neuron loss and brain atrophy by eight to 12 months, especially in the hippocampus and spreading to the neocortex and entorhinal cortex. Neurofibrillary tangles in the neocortex, amygdala, hippocampus, brain stem, and spinal cord. Neuroinflammation with microgliosis and astrocytosis. Impairments in spatial memory and learning ability in Morris water maze. Paralysis at seven to 10 months associated with a hunched-back posture followed by feeding difficulties. About 80 percent mortality by 12 months with median survival of about nine months. Clasping and limb retraction when lifted by the tail at three months, followed by limb weakness and brain atrophy. Homozygous females do not mate. The Jackson Lab: Stock# 008169; Live. Research with this model is available from Scantox Neuro. Yoshiyama et al., 2007 Yes
<p>-</p>, <p>Triple transgenic</p>, <p>3Tg</p> B6.D2-Tg(Thy1-APPSwe, Prp-PSEN2N141I, Thy1-TauP301L) C57BL/6, DBA/2; backcrossed to C57BL/6 APP, MAPT, PSEN2 APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I 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
<p>APPSwe-Tau</p>, <p>APPSwe(2576)/TauJNPL3</p>, <p>TAPP</p> Tg(APPSWE)2576Kha; Tg(Prnp-MAPT*P301L)JNPL3Hlmc C57BL/6, DBA/2, SJL, SW Mixed Background APP, MAPT APP K670_M671delinsNL (Swedish), MAPT P301L Generated by crossing Tg2576 mice, which have the transgene for human APP (isoform 695) carrying the Swedish mutation with mice expressing human MAPT (4 repeat) with the P301L mutation. APP; MAPT: Transgenic Alzheimer's Disease Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis. Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming. Progressive hindlimb weakness. Hunched posture. Eye irritations. Some mice have the Pde6brd1 retinal degeneration mutation which can cause light sensitivity and/or blindness and may affect behavioral testing. Taconic: Stock# 2469 Lewis et al., 2001 Yes
<p>-</p>, <p>Tau22</p> C57BL6/CBA; backcrossed to C57BL6 MAPT MAPT G272V, MAPT P301S Transgene containing the cDNA of the 412 amino acid isoform of human 4-repeat tau mutated at sites G272V and P301S under a Thy1.2 promotor. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease A variety of tau pathologies starting at 3 months, including neurofibrillary tangle-like inclusions, rare ghost tangles, and paired helical filament-like structures. Hyperphosphorylation of tau on many epitopes (e.g. AT8, AT100, AT180, AT270, 12E8, tau-pSer396, and AP422) and mild astrogliosis. Increased anxiety and delayed learning from 3 months, and reduced spatial memory at 10 months. No changes in overall motor activity and no gross motor deficits. Increased depression-like and aggressive behavior, co-occurring with disturbances in nocturnal activity. Fertile with normal frequency and size of litters. Stably transmits the transgene to offspring. Deficits in hippocampal synaptic transmission. Available through Luc Buée Schindowski et al., 2006 Yes
<p>-</p>, <p>Trem2<sup>-/-</sup>PS19</p> C57BL/6 -TREM2tm1cln; B6;C3-Tg(Prnp-MAPT*P301S)PS19Vle/J C57BL/6 Trem2, MAPT MAPT P301S Trem2 KO (Colonna) mice were crossed with PS19 mice. TREM2 KO: Inactivation of the mouse Trem2 gene was achieved by targeted deletion of exons 3 and 4. PS19: express human MAPT (1N4R) with the P301S mutation, driven by the mouse prion protein (Prnp) promoter. Trem2: Knock-Out; MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Microgliosis, astrogliosis, and brain atrophy in Trem2-/-PS19 mice are greatly attenuated compared with Trem2+/+PS19 animals. No data. Trem2 KO: available through Marco Colonna. PS19: The Jackson Lab: Stock# 008169; Live Leyns et al., 2017 Yes
Rat Models (1)
Sprague-Dawley MAPT MAPT P301S Tg12099 rats express the 0N4R isoform of human MAPT with P301S mutation linked to frontotemporal dementia, driven by the rat Prnp promoter. MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease Tau pathology, including neurofibrillary tangles, forebrain neurodegeneration, and astrogliosis in homozygotes. Hemizygotes exhibit little pathology, save for a few AT8-immunoreactive neurons in the entorhinal cortices of aged animals. Ataxia, bradykinesia, and seizures reported in aging homozygotes. Premature death of homozygotes, with median survival of 14 months. Contact David Westaway, Institute for Neurodegenerative Diseases, UCSF. Ayers et al., 2024 Yes

23 Visualizations

AD-related Research Models

Phenotypes Examined

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

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

3xTg

Observed
  1. X
    Plaques at 26

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

  2. X
    Tangles at 52

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

  3. X
    Gliosis at 30

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

  4. X
    Changes in LTP/LTD at 26

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

  5. X
    Cognitive Impairment at 17

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

Absent
No Data
  • Neuronal Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Psen1, APP, MAPT APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN1 M146V Psen1: Knock-In; APP: Transgenic; MAPT: Transgenic Alzheimer's Disease

Age-related, progressive neuropathology including plaques and tangles. Extracellular Aβ deposits by 6 months in frontal cortex, more extensive by 12 months. No tau pathology at 6 months, but evident at 12 months. Synaptic dysfunction, including LTP deficits, prior to plaques and tangles.

Cognitive impairment by 4 months. Impairments first manifest as a retention/retrieval deficit and not as a learning deficit, and occur prior to plaques and tangles. Deficits in both spatial and contextual based paradigms. Clearance of intraneuronal Aβ by immunotherapy rescues the early cognitive deficits in a hippocampal-dependent task.

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AAV-sTREM2 PS19

Observed
  1. X
    Synaptic Loss at 28

    AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.

  2. X
    Changes in LTP/LTD at 29

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

  3. X
    Cognitive Impairment at 30

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

Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
TREM2, MAPT MAPT P301S TREM2: Virus; MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

AAV-mediated expression of sTREM2 protected against hippocampal synapse loss in PS19 mice.

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

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hTau.P301S

Observed
  1. X
    Tangles at 17

    Neurofibrillary tangles detected as early as 4 months of age.

  2. X
    Neuronal Loss at 13

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

  3. X
    Gliosis at 22

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

  4. X
    Cognitive Impairment at 11

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

Absent
  • Plaques at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301S MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

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

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

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JNPL3(P301L)

Observed
  1. X
    Tangles at 20

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

  2. X
    Neuronal Loss at 43

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

  3. X
    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.

No Data
  • Cognitive Impairment at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Transgenic Frontotemporal Dementia, Progressive Supranuclear Palsy, Alzheimer's Disease

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

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

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MAPT 10IVS+16 C&gt;T

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, MAPT-AS1, Mapt MAPT IVS10+16 C>T MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Frontotemporal Dementia

Unknown.

Unknown.

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MAPT(H1.0)-GR

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

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

Unknown.

Unknown.

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MAPT(H1.0*N279K)-GR

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, MAPT-AS1, Mapt MAPT N279K MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Frontotemporal Dementia

Unknown.

Unknown.

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MAPT(H1.0*)P301L-GR

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, MAPT-AS1, Mapt MAPT P301L MAPT: Knock-In; MAPT-AS1: Knock-In; Mapt: Knock-Out Frontotemporal Dementia

Unknown.

No overt behavioral phenotypes

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MAPT(H2.1)-GR

Observed
Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

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

Unknown.

Unknown.

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PLB1-triple (hAPP/hTau/hPS1)

Observed
  1. X
    Gliosis at 52

    Increased inflammation (GFAP labelling) detected at 12 months in cortex and hippocampus (Platt, unpublished observation).

  2. X
    Changes in LTP/LTD at 26

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

  3. X
    Cognitive Impairment at 22

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

Absent
  • Plaques at

    Sparse plaques out to 21 months of age. Only marginally increased compared with wild-types and overall very low compared to over-expression models. However, Aβ accumulated intracellularly and also formed oligomers.

  • Tangles at

    No overt tangle pathology; however, hyyperphosphorylated tau accumulated in the hippocampus and cortex from six months of age.

  • Neuronal Loss at

    Absent.

No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, MAPT, PSEN1 APP V717I (London), APP K670_M671delinsNL (Swedish), PSEN1 A246E, MAPT P301L, MAPT R406W APP: Multi-transgene; MAPT: Multi-transgene; PSEN1: Multi-transgene Alzheimer's Disease

Age-related neuropathology including intraneuronal and oligomeric Aβ accumulation and hyperphosphorylated tau in the hippocampus and cortex from six months. Minimal amyloid plaques up to 21 months. Subtle tau pathology, but no overt tangles. Cortical hypometabolism with increased metabolic activity in basal forebrain and ventral midbrain by FDG-PET/CT.

Cognitive deficits in recognition memory and spatial learning emerging between five and 12 months. Impairments in hippocampal plasticity.

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PS19 with humanized TREM2 (common variant)

Observed
  1. X
    Tangles at 37

    Tangles revealed using antibody PG5 at 9 months.

  2. X
    Neuronal Loss at 38

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

  3. X
    Gliosis at 39

    Elevated expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the R47H variant of TREM2.

  4. X
    Synaptic Loss at 40

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

Absent
No Data
  • Plaques at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, TREM2, Trem2 MAPT P301S MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia

Brain atrophy by 9 months of age. Increased microgliosis, astrogliosis and synapse loss, compared with PS19 mice carrying TREM2 with the R47H mutation.

Not known.

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PS19 with humanized TREM2 (R47H)

Observed
  1. X
    Tangles at 36

    Tangles revealed using antibody PG5 at 9 months.

Absent
No Data
  • Plaques at

    No data.

  • Neuronal Loss at

    No data relative to wild-type mice, but at 9 months of age, the volumes of the hippocampus and entorhinal/piriform cortex are larger, and the granule cell layer of the dentate gyrus and pyramidal cell layer of the piriform cortex are thicker, in PS19-TREM2R47H mice, compared with PS19 mice carrying the common variant of human TREM2.

  • Gliosis at

    At 9 months of age, decreased expression of markers of astroglial and microglial reactivity, compared with PS19 mice carrying the common variant of TREM2, but no data relative to wild-type mice.

  • Synaptic Loss at

    At 9 months of age, more synapses and fewer dystrophic synapses, compared with PS19 mice carrying the common variant of TREM2, but no data relative to wild-type mice.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT, TREM2, Trem2 MAPT P301S, TREM2 R47H MAPT: Transgenic; TREM2: Transgenic; Trem2: Knock-Out Alzheimer's Disease, Frontotemporal Dementia

Decreased brain atrophy, microgliosis, astrogliosis, and synapse loss, compared with PS19 mice carrying the common variant of TREM2.

Not known.

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rTgTauEC

Observed
  1. X
    Tangles at 78

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

  2. X
    Neuronal Loss at 83

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

  3. X
    Gliosis at 104

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

  4. X
    Synaptic Loss at 104

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

  5. X
    Changes in LTP/LTD at 70

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

  6. X
    Cognitive Impairment at 70

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

Absent
  • Plaques at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

Propagating tau pathology starting in the entorhinal cortex and spreading to regions functionally connected to the EC (e.g., dentate gyrus). Neurodegeneration and axonal degeneration, first in EC and parasubiculum. Gliosis and synaptic loss.

Subtle cognitive deficit in contextual fear conditioning, but not in the radial arm maze, at 16 months. Mild specific deficit in locomotor activity in the open field test.

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rTg(tauP301L)4510

Observed
  1. X
    Tangles at 17

    Pretangles as early as 2.5 months. Argyrophilic tangle-like inclusions in cortex by 4 months and in hippocampus by 5.5 months.

  2. X
    Neuronal Loss at 24

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

  3. X
    Synaptic Loss at 35

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

  4. X
    Cognitive Impairment at 11

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

Absent
  • Plaques at

    Absent.

No Data
  • Changes in LTP/LTD at

    LTP at the Schaffer collateral-CA1 synapse is normal at 1.3 months, but impaired at 4.5 months.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

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

Spatial memory impairments by 2.5 to 4 months. No significant motor impairment up to 6 months of age. When the transgene was suppressed with dox at 2.5 months, spatial memory improved.

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TauA152T-AAV

Observed
  1. X
    Neuronal Loss at 10

    Neuron loss in cortex, seen at 3 months.

  2. X
    Gliosis at 11

    Astrogliosis, but not microgliosis, seen at 3 months.

  3. X
    Cognitive Impairment at 12

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

Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT A152T MAPT: Virus Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Neuron loss and astrogliosis were observed in the cortices of 3-month-old mice.

Compared with GFP-AAV controls, TauA152T-AAV mice showed deficits in contextual and cued fear conditioning, increased hyperactivity, and decreased rearing in the open-field test, and spent more time in the open arms of the elevated plus maze. TauA152T-AAV mice also exhibited motor impairment on the Rotarod.

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Tau P301L

Observed
  1. X
    Tangles at 35

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

  2. X
    Gliosis at 30

    Astrogliosis by 7 months.

  3. X
    Changes in LTP/LTD at 26

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

  4. X
    Cognitive Impairment at 22

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

Absent
  • Plaques at

    Absent.

No Data
  • 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 Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

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

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

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TauP301L-AAV

Observed
  1. X
    Tangles at 24

    Argyrophilic, Thioflavin S-positive neurofibrillary tangles in cortex and hippocampus.

  2. X
    Gliosis at 12

    Astrogliosis and microgliosis observed at 3 months.

  3. X
    Cognitive Impairment at 24

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

Absent
  • Neuronal Loss at

    No cortical neuron loss at 6 months.

No Data
  • Plaques at

    No data.

  • Synaptic Loss at

    The accumulation of a PSD95 fragment suggests the possibility of synaptic abnormalities, although synaptic structure and function have not been assessed directly.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301L MAPT: Virus Alzheimer's Disease, Frontotemporal Dementia, Other Tauopathy

Neurofibrillary tangles and gliosis, but no cortical neuron loss, at 6 months of age.

Hyperactivity in the open field, decreased time spent in the center of open field, more time spent in the open arms of the elevated plus maze, and deficits in cued and contextual fear conditioning at 6 months of age.

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Tau P301S (Line PS19)

Observed
  1. X
    Tangles at 23

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

  2. X
    Neuronal Loss at 39

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

  3. X
    Gliosis at 11

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

  4. X
    Synaptic Loss at 13

    Synaptophysin immunoreactivity decreased progressively from three to six months in the CA3 region of the hippocamus. Impaired synaptic function (Yoshiyama et al., 2007).

  5. X
    Changes in LTP/LTD at 26

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

  6. X
    Cognitive Impairment at 27

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

Absent
  • Plaques at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301S MAPT: Transgenic Alzheimer's Disease, Frontotemporal Dementia

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

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

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TauPS2APP

Observed
  1. X
    Plaques at 17

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

  2. X
    Tangles at 70

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

  3. X
    Cognitive Impairment at 17

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

Absent
  • Neuronal Loss at

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

No Data
  • Gliosis at

    Unknown.

  • Synaptic Loss at

    Unknown.

  • Changes in LTP/LTD at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, MAPT, PSEN2 APP K670_M671delinsNL (Swedish), MAPT P301L, PSEN2 N141I APP: Transgenic; MAPT: Transgenic; PSEN2: Transgenic Alzheimer's Disease

Phosphorylated tau accumulation in the subiculum and the CA1 region of the hippocampus at 4 months. Neurofibrillary tangles in these regions as well as the amygdala. Amyloid plaques. Dystrophic neurites and neuropil threads containing abnormally phosphorylated tau. No overt neuronal loss.

Impaired spatial learning in the Morris water maze at 4 months but impairment is not progressive between 4 and 12 months and appears to be independent of pathology.

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Tg12099 rat

Observed
  1. X
    Tangles at 26

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

  2. X
    Neuronal Loss at 39

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

  3. X
    Gliosis at 27

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

Absent
No Data
  • Plaques at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT P301S MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

Tau pathology, including neurofibrillary tangles, forebrain neurodegeneration, and astrogliosis in homozygotes. Hemizygotes exhibit little pathology, save for a few AT8-immunoreactive neurons in the entorhinal cortices of aged animals.

Ataxia, bradykinesia, and seizures reported in aging homozygotes.

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Tg2576/Tau(P301L) (APPSwe-Tau)

Observed
  1. X
    Plaques at 39

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

  2. X
    Tangles at 13

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

  3. X
    Gliosis at 13

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

Absent
No Data
  • Synaptic Loss at

    Unknown.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, MAPT APP K670_M671delinsNL (Swedish), MAPT P301L APP; MAPT: Transgenic Alzheimer's Disease

Gradual appearance of plaques; by 9 months plaques are scattered throughout the cortex, hippocampus, and amygdala similar to Tg2576. Tau pathology more extensive than JNPL3. Astrocytosis and microgliosis.

Motor disturbances similar to JNPL3, with identical range in age of onset. Reduced vocalization and decreased grooming.

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THY-Tau22

Observed
  1. X
    Tangles at 13

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

  2. X
    Neuronal Loss at 52

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

  3. X
    Gliosis at 13

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

  4. X
    Changes in LTP/LTD at 39

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

  5. X
    Cognitive Impairment at 26

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

Absent
  • Plaques at

    Absent.

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
MAPT MAPT G272V, MAPT P301S MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

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

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

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Trem2 KO (Colonna) x PS19

Observed
  1. X
    Gliosis at 36

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

Absent
No Data
  • Plaques at

    No data.

  • Tangles at

    No data.

  • Neuronal Loss at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

  • Cognitive Impairment at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
Trem2, MAPT MAPT P301S Trem2: Knock-Out; MAPT: Transgenic Frontotemporal Dementia, Alzheimer's Disease

Microgliosis, astrogliosis, and brain atrophy in Trem2-/-PS19 mice are greatly attenuated compared with Trem2+/+PS19 animals.

No data.

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