Research Models
Selected Results
10 Models
Name | Other Names | Strain Name | Genetic Background | Gene | Mutation | Modification Info | Modification | Disease | Neuropathology | Behavior/Cognition | Other Phenotype | Availability | Primary Paper | Visualization | |
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Mouse Models (10) |
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5XFAD, APP/PS1, Tg6799, Tg-5xFAD | B6SJL-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmjax | C57BL/6 x SJL | APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Two transgenes: mutant human APP with the APP Swedish, Florida, and London mutations and containing the 5' untranslated region driven by the mouse Thy1 promoter; and mutant human PSEN1 including the M146L and L286V mutations driven by the mouse Thy1 promoter. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles. | Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype. | The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live. | Oakley et al., 2006 | Yes | |||
APOE2-FAD, APOE2 Targeted Replacement x 5xFAD | C57BL/6 | APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE2 Targeted Replacement mice were crossed with the 5xFAD line. | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. | In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice. | 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE2 Targeted Replacement mice are available through Taconic, Stock# 1547-F or 1547-M. | Youmans et al., 2012 | Yes | ||||
APOE3-FAD, APOE3 Targeted Replacement x 5xFAD | C57BL/6 | APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE3 Targeted Replacement mice were crossed with the 5xFAD line. | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. | In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice. | 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE3 Targeted Replacement mice are available through Taconic, Stock# 1548-F or 1548-M. | Youmans et al., 2012 | Yes | ||||
APOE4-FAD, APOE4 Targeted Replacement x 5xFAD | C57BL/6 | APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE4 Targeted Replacement mice were crossed with the 5xFAD line. | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. | Age-dependent learning and memory deficits in the Y maze and Morris water maze. | 5xFAD mice are available through The Jackson Lab, Stock# 034840; Live. APOE4 Targeted Replacement mice are available through Taconic, Stock# 1549-F or 1549-M. | Youmans et al., 2012 | Yes | ||||
PSEN1(M146L), PS1 (M146L) line 5.1 | B6/D2/Swe/SJL mixed background | PSEN1 | PSEN1 M146L (A>C) | Transgene containing human PSEN1 with the M146L mutation driven by the rat PDGF-β promoter. | PSEN1: Transgenic | Alzheimer's Disease | No abnormal pathology up to 2.5 years. Elevated Aβ2(43); no effect on Aβ40. Altered mitochondrial activity. Disregulation of calcium homeostasis. | No difference from wild-type mice in the “Y” maze (alternation performance or activity) at 12-14 weeks. | Elevated PSEN1 expression (2-3 fold). Medium and late after hyperpolarizations in CA3 pyramidal cells were larger compared with wild-type mice. Larger calcium responses to depolarization. Stronger synaptic potentiation of the CA3 to CA1 projection. | Available through the Technology Transfer Office, Patents & Licensing, University of South Florida. The CRO PsychoGenics offers research services with this line. | Duff et al., 1996 | No | |||
PS1 + APP, PSAPP, APP/PS1, APP/PS1 double transgenic | B6/D2/Swe/SJL mixed background | APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C) | These double transgenic mice were generated by crossing mice overexpressing human APP with the Swedish mutation driven by the hamster prion protein gene promoter (the Tg2576 model) with mice overexpressing human PSEN1 with the M146L mutation driven by the PDGF-β promoter (PSEN1(M146L), line 5.1). The two transgenes segregate independently. | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter, cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation. | Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels. | Selective increase in brain Aβ42(43) in the double transgenics (41% increase at 6 weeks) compared to Tg2576 single transgenic, which had unchanged Aβ40 and Aβ42(43) at this age. | Tg2576: Taconic (Stock #001349) and Charles River; PS1(M146L): University of South Florida Technology Transfer Office. The CRO PsychoGenics offers research services with Tg2576 and the double transgenic line. | Holcomb et al., 1998 | Yes | |||
BAC-TREM2 X 5xFAD | TREM2-BAC: FVB/NJ; 5xFAD: C57BL/6 X SJL | TREM2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | TREM2-BAC mice were crossed with 5xFAD mice. | TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques with plaque-associated microgliosis. Reduced plaque burden, altered microglial and plaque morphology, and less severe plaque-associated neuritic dystrophy, compared with 5xFAD. | 5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired. | TREM2-BAC: Available through X. William Yang. 5xFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034840; Live | Lee et al., 2018 | Yes | ||||
CV+mTrem2−/−5XFAD | C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 | Trem2, TREM2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | BAC transgenic mice carrying human TREM2 (common variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the common variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5xFAD mice. | Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques surrounded by activated microglia. | No data. | Neurodegeneration-associated microglial activation markers elevated, compared with 5XFAD lacking TREM2. | TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live | Song et al., 2018 | Yes | |||
R47H+mTrem2−/−5XFAD | C57BL/6 X CBA, back-crossed for at least 4 generations to C57BL/6 | Trem2, TREM2, APP, PSEN1 | TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | BAC-transgenic mice carrying the human TREM2 (R47H variant), TREML1, and TREML2 were back-crossed to Trem2 KO mice (Colonna) to yield mice that express the R47H variant of human TREM2 in the absence of mouse Trem2. These mice were then crossed with 5XFAD mice. | Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant. | No data. | TREM2 mice: available through Marco Colonna; 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live | Song et al., 2018 | Yes | ||||
Trem2-/-5XFAD, mTrem2-/-5XFAD | C57BL/6 -TREM2tm1cln; B6.Cg-Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/Mmja | C57BL/6 | Trem2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | 5XFAD mice were crossed with Trem2 KO mice. TREM2 KO: Targeted deletion of exons 3 and 4 of mouse Trem2. 5XFAD express two transgenes: 1) human APP with the Swedish, Florida and London mutations, containing the 5' untranslated region and driven by the mouse Thy1 promoter and 2) human PSEN1 with the M146L and L286V mutations driven by the mouse Thy1 promoter. | Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes. | No data. | Trem2 KO: available through Marco Colonna. 5XFAD: The Jackson Lab; available through the JAX MMRRC Stock# 034848; Live | Wang et al., 2015 | Yes |
9 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+.
5xFAD (B6SJL)
Observed
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Plaques at 8
Extracellular amyloid deposition begins around 2 months, first in the subiculum and layer V of the cortex. Aβ42 also accumulates intraneuronally in an aggregated form within the soma and neurites starting at 1.5 months.
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Neuronal Loss at 24
Neuron loss in cortical layer V and subiculum.
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Gliosis at 8
Gliosis begins at 2 months.
-
Synaptic Loss at 16
Levels of the presynaptic marker synaptophysin begin to decline by 4 months; levels of syntaxin, another presynaptic marker, and PSD-95, a postsynaptic marker, decline by 9 months
-
Changes in LTP/LTD at 24
Basal synaptic transmission and LTP in hippocampal area CA1 begin to deteriorate between 4 and 6 months
-
Cognitive Impairment at 18
Impaired spatial working memory in the Y-maze test and impaired remote memory stabilization in a contextual-fear-conditioning test by 4 to 5 months of age.
Absent
-
Tangles at
Absent.
No Data
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid pathology starting at 2 months, including amyloid plaques. Accumulation of intraneuronal Aβ before amyloid deposition. Gliosis and synapse degeneration. Neuron loss in cortical layer 5 and subiculum. No neurofibrillary tangles. |
Age-dependent memory deficits including spatial memory, stress-related memory, and memory stablization. Motor phenotype. |
E2FAD
Observed
-
Plaques at 17
Plaques develop in the subiculum and deep cortical layers by 4 months.
-
Gliosis at 26
Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
-
Synaptic Loss at 17
Protein levels of NMDA receptor subunits decreased from 2 to 6 months.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
E2FAD mice had performance in learning and memory tasks comparable to E3FAD animals and better than E4FAD mice.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. |
In the Y maze and Morris water maze, E2FAD mice performed better than E4FAD mice, and were comparabile to E3FAD mice. |
E3FAD
Observed
-
Plaques at 17
Plaques develop in the subiculum and deep cortical layers by 4 months.
-
Gliosis at 26
Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
-
Synaptic Loss at 17
Protein levels of NMDA receptor subunits decreased from 2 to 6 months.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Changes in LTP/LTD at
No data.
-
Cognitive Impairment at
E3FAD mice had performance in learning and memory tasks comparable to E4FAD and E2FAD animals.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. |
In the Y maze and Morris water maze E3FAD mice performed better than E4FAD mice, and were comparabile to E2FAD mice. |
E4FAD
Observed
-
Plaques at 17
Plaques develop in the subiculum and deep cortical layers by 4 months.
-
Gliosis at 26
Microgliosis and astrocytosis in the subiculum and cortex at 6 months.
-
Synaptic Loss at 17
Decreased protein levels of PSD95 and NMDA receptor subunits by 4 months.
-
Cognitive Impairment at 8
Modest learning deficits in the Morris water maze by 2 months. Progressive decrease in performance on learning and memory tasks.
Absent
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APOE, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | APOE: Knock-In; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques starting at 4 months and increasing with age. Gliosis and loss of synaptic proteins. |
Age-dependent learning and memory deficits in the Y maze and Morris water maze. |
PS/APP
Observed
-
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).
-
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).
-
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).
-
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).
No Data
-
Synaptic Loss at
Unknown.
-
Changes in LTP/LTD at
Unknown.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
APP, PSEN1 | APP K670_M671delinsNL (Swedish), PSEN1 M146L (A>C) | APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Aβ accumulates in the cerebral cortex and hippocampus starting ~6 months and increasing with age. Other regions affected later. Deposition occurs in white matter, cerebrovasculature, and grey matter in the form of diffuse and fibrillar plaques. Fibrillar deposits are associated with dystrophic neurites and GFAP-positive astrocytes at ~ 6 months with later microglial activation. |
Progressive impairment between 5–7 and 15–17 months in some tests of cognitive performance, but not others. No change in anxiety levels. |
TREM2-BAC X 5xFAD
Observed
-
Plaques at 28
Observed at 7 months, the youngest age examined.
-
Gliosis at 28
Microgliosis observed; however, fewer plaque-associated microglia and altered microglial morphology (more ramified processes) compared with 5xFAD at 7 months, the only age examined.
Absent
-
Cognitive Impairment at
5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired.
No Data
-
Tangles at
No data.
-
Neuronal Loss at
No data.
-
Synaptic Loss at
No data.
-
Changes in LTP/LTD at
No data.
Genes | Mutations | Modification | Disease | Neuropathology | Behavior/Cognition |
---|---|---|---|---|---|
TREM2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques with plaque-associated microgliosis. Reduced plaque burden, altered microglial and plaque morphology, and less severe plaque-associated neuritic dystrophy, compared with 5xFAD. |
5xFAD/TREM2 mice perform comparably to wild-type mice in a contextual fear conditioning test, while 5xFAD mice are impaired. |
TREM2, humanized (common variant) X 5XFAD
Observed
-
Plaques at 34
Plaques observed in 8.5-month-old mice, only age reported thus far.
-
Gliosis at 34
Microgliosis observed in 8.5-month-old mice, only age reported thus far.
Absent
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, TREM2, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Amyloid plaques surrounded by activated microglia. |
No data. |
TREM2, humanized (R47H) X 5XFAD
Observed
-
Plaques at 34
Plaques observed in 8.5-month-old mice, the only age reported thus far.
-
Gliosis at 34
Microgliosis observed in 8.5-month-old mice, the only age reported thus far. Fewer plaque-associated microglia in mice expressing the R47H variant, compared with the common variant of human TREM2.
Absent
No Data
-
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, TREM2, APP, PSEN1 | TREM2 R47H, APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Trem2: Knock-Out; TREM2: Transgenic; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Lower density of activated microglia surrounding amyloid plaques in 5XFAD mice expressing the R47H variant of human TREM2 compared with those expressing the common variant. |
No data. |
Trem2 KO (Colonna) x 5XFAD
Observed
-
Plaques at 16
Plaques present by 4 months, the earliest age studied.
-
Neuronal Loss at 32
Loss of cortical layer V neurons by 8 months, the earliest age studied.
-
Gliosis at 16
MIcrogliosis by 4 months, the earliest age studied.
Absent
No Data
-
Tangles 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, APP, PSEN1 | APP K670_M671delinsNL (Swedish), APP I716V (Florida), APP V717I (London), PSEN1 M146L (A>C), PSEN1 L286V | Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic | Alzheimer's Disease | Compared with 5XFAD, mice deficient in TREM2 show an age- dependent increase in amyloid accumulation in the hippocampus, more severe plaque-associated neuritic dystrophy, and exaggerated neuron loss in the cortex. Microglial containment of plaques is compromised in TREM2-deficient animals. Microglia accumulate autophagosomes. |
No data. |