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3 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 (3)
<p>-</p>, <p>B6-Tg/Thy1APP23Sdz</p> B6.Cg-Tg(Thy1-APP)3Somm/J C57BL/6 APP APP K670_M671delinsNL (Swedish) Transgene containing human APP (isoform 751) containing the Swedish (KM670/671NL) mutation under the murine Thy1 promoter. APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy Aβ deposits first observed at 6 months. Congophilic plaques increase in size and number with age and are surrounded by activated microglia, astrocytes, and dystrophic neurites containing hyperphosphorylated tau (although no neurofibrillary tangles). Neuronal loss in the CA1 region of the hippocampus. Mice also develop CAA, and microhemorrages occur at later ages. Spatial memory defects in Morris Water maze at 3 months and progresses with age. Memory deficits in passive avoidance were observed in 25 month-old mice, but not at younger ages. Hyperactivity observed between the ages of 6 weeks to 6 months. It is not known whether this persists or resolves in older animals. Abnormalities in open field test and impaired performance on rotorod observed from 3 months. Available through The Jackson Laboratory Stock# 030504, Live Sturchler-Pierrat et al., 1997 Yes
B6.Cg-Tg(Thy1-APP)3Somm/J; Psen1tm1.1Tcs C57BL/6J APP, PSEN1 PSEN1 R278I This is a cross between APP23 mice, which overexpress APP751 with the Swedish mutation driven by the murine Thy1 promoter, and PSEN1 knock-in mice expressing human PSEN1 with the R278I mutation under the endogenous promoter. APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques. Short-term memory deficits apparent by 3-4 months as measured by the Y maze. Reduced γ-secretase activity. Available through Takaomi Saido Saito et al., 2011 Yes
<p>-</p>, <p>TREM2-IPDxAPP23xPS45</p>, <p>APP23xPS45xIPD</p> C57BL/6 Trem2, APP, PSEN1 APP K670_M671delinsNL (Swedish), PSEN1 G384A Trem2-IPDxAPP23xPS45 mice have a modified murine Trem2 gene (resulting in disruption of the ADAM protease cleavage site after amino acid 157) and carry transgenes for human APP and PSEN1 with the AD-linked Swedish and G384A mutations, respectively. Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, plaque-associated neuritic dystrophies, microgliosis. Pathology exacerbated in Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 mice expressing wild-type Trem2, at an early—but not late—stage of plaque deposition. Unknown. Microglial maturation accelerated in Trem2-IPDxAPP23xPS45  mice, compared with APP23xPS45 mice expressing wild-type Trem2. TREM2-IPD and PS45 mice are available from Novartis Pharma AG under an MTA. Contact Ivan Galimberti (ivan.galimberti@novartis.com) or Derya Shimshek (derya.shimshek@novartis.com). APP23 mice are available through The Jackson Laboratory Stock# 030504, Live. Dhandapani et al., 2022 Yes

3 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+.

APP23

Observed
  1. X
    Plaques at 26

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

  2. X
    Neuronal Loss at 61

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

  3. X
    Gliosis at 26

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

  4. X
    Cognitive Impairment at 13

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

Absent
  • 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).

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP APP K670_M671delinsNL (Swedish) APP: Transgenic Alzheimer's Disease, Cerebral Amyloid Angiopathy

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

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

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APP23 x PS1-R278I

Observed
  1. X
    Plaques at 26

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

  2. X
    Gliosis at 39

    Astrocytosis in the vicinity of plaques in the hippocampus and cortex by 9 months.

  3. X
    Cognitive Impairment at 13

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

Absent
  • Tangles at

    Not observed.

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
APP, PSEN1 PSEN1 R278I APP: Transgenic; PSEN1: Knock-In Alzheimer's Disease

Amyloid deposition by 6 months of age in the cortex and hippocampus. Abundant reactive astrocytes in the vicinity of plaques. Elevated Aβ43 in the brain by 3 months. High density of cored plaques. Pyroglutamate Aβ (N3pE-Aβ) associated with amyloid plaques.

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

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Trem2-IPDxAPP23xPS45

Observed
  1. X
    Plaques at 12

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

  2. X
    Gliosis at 13

    Increased microgliosis in the vicinity of plaques in 3-month-old Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 mice.

  3. X
    Synaptic Loss at 14

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

Absent
No Data
  • Tangles at

    No data.

  • Neuronal 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), PSEN1 G384A Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, plaque-associated neuritic dystrophies, microgliosis. Pathology exacerbated in Trem2-IPDxAPP23xPS45 mice, compared with APP23xPS45 mice expressing wild-type Trem2, at an early—but not late—stage of plaque deposition.

Unknown.

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