Research Models

Selected Results

4 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)
APPPS1-21 B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr 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
APPPS1;Trem2-/- TREM2tm1(KOMP)Vlcg; B6.Cg-Tg(Thy1-APPSw,Thy1-PSEN1*L166P)21Jckr C57BL/6 Trem2, APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 L166P Trem2-/-: The entire coding region of the Trem2 gene was replaced by Velocigene cassette ZEN-Ub1 (lacZ-p(A)-loxP-hUbCpro-neor-p(A)-LoxP). APPPS1: Mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter. Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Reduced plaque burden at early stages of plaque deposition but increased plaque burden at later stages, fewer plaque-associated myeloid cells and astrocytes, less phospho-tau in plaque-associated dystrophic neurites, compared with APPPS1. No data. APPPS1 available through Mathias Jucker; Trem2 KO available through UC Davis KOMP Repository, Project VG10093, cryo-recovery or sperm Jay et al., 2015, Jay et al., 2017 Yes
APPPS1-21;Trem2+/R47H C57BL6/J Trem2, APP, PSEN1 TREM2 R47H, APP KM670/671NL (Swedish), PSEN1 L166P To create Trem2+/R47H mice, CRISPR/Cas9 was used to introduce the R47H variant into the endogenous mouse Trem2 gene. APPPS1-21 mice express human APP with the Swedish (K670M/N671L) mutations and human PSEN1 with the L166P mutation, both under control of the Thy1 promoter. Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, fewer plaque-associated myeloid cells, and worse plaque-associated neuritic dystrophy, compared with APPPS1-21 mice homozygous for wild-type Trem2. Unknown. Levels of Trem2 transcripts were reduced in APPPS1-21;Trem2+/R47H compared with APPPS1-21;Trem2+/+ and were similar to those in APPPS1-21 mice haploinsufficient for Trem2. Trem2+/R47H available through Gary Landreth or Bruce Lamb; APPPS1-21 available through Mathias Jucker. Cheng-Hathaway et al., 2018 Yes
Rat Models (1)
Fischer 344 APP, PSEN1 APP KM670/671NL (Swedish), APP V717F (Indiana), PSEN1 L166P APP+PS1 transgenic rats express human APP with the Swedish and Indiana mutations and human PSEN1 with the L166P mutation. Both transgenes are driven by the ubiquitin-C promoter. APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age. Deficits in Barnes maze by 10 months of age. Agca et al., 2016, Klakotskaia et al., 2018 Yes

4 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+.

APPPS1

Observed
  1. X
    Plaques at 6

    Aβ deposition begins at 6 weeks of age in the cortex and 3-4 months of age in the hippocampus (Radde et al., 2006).

  2. X
    Neuronal Loss at 74

    Global neuron loss is not observed, but modest neuron loss was found in the granule cell layer of the dentate gyrus and other subregions with high neuronal density in 17-month old animals (Rupp et al., 2011).

  3. X
    Gliosis at 6

    Activated microglia around Aβ deposits at 6 weeks as well as increased astrogliosis (Radde et al., 2006). Levels of CCL2 and TNFα increase at later ages (Lee et al., 2010).

  4. X
    Synaptic Loss at 10

    Dendritic spine loss around plaques reported to begin approximately 4 weeks after plaque formation and continue for several months (Bittner et al., 2012).

  5. X
    Changes in LTP/LTD at 35

    Hippocampal CA1 LTP normal at 4.5 months of age, but impaired at 8 and 15 months of age (Gengler et al., 2010).

  6. X
    Cognitive Impairment at 30

    Cognitive deficits in spatial learning and memory in the Morris water maze reported at 7 months (Serneels et al., 2009). Impaired reversal learning of a food-rewarded four-arm spatial maze task observed at 8 months (Radde et al., 2006).

Absent
  • Tangles at

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

No Data
Genes Mutations Modification Disease Neuropathology Behavior/Cognition
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.

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APP+PS1

Observed
  1. X
    Plaques at 76

    Abundant plaques in hippocampus and subiculum, scattered plaques in cortex.

  2. X
    Neuronal Loss at 76

    Necrotic neurons in hippocampus and cortex.

  3. X
    Cognitive Impairment at 40

    Deficits in Barnes maze at 10 months.

Absent
No Data
  • Tangles at

    No data.

  • Gliosis at

    No data.

  • Synaptic Loss at

    No data.

  • Changes in LTP/LTD at

    No data.

Genes Mutations Modification Disease Neuropathology Behavior/Cognition
APP, PSEN1 APP KM670/671NL (Swedish), APP V717F (Indiana), PSEN1 L166P APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Amyloid plaques, cerebral amyloid angiopathy, and necrotic neurons in hippocampus and cortex by 19 months of age.

Deficits in Barnes maze by 10 months of age.

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Trem2 KO (KOMP) x APPPS1

Observed
  1. X
    Plaques at 9

    Plaques are observed by 2 months.

  2. X
    Gliosis at 9

    Gliosis is observed by 2 months.

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, APP, PSEN1 APP KM670/671NL (Swedish), PSEN1 L166P Trem2: Knock-Out; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Reduced plaque burden at early stages of plaque deposition but increased plaque burden at later stages, fewer plaque-associated myeloid cells and astrocytes, less phospho-tau in plaque-associated dystrophic neurites, compared with APPPS1.

No data.

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Trem2 R47H KI (Lamb/Landreth) X APPPS1-21

Observed
  1. X
    Plaques at 16

    Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, compared with APPPS1-21 mice homozygous for wild-type Trem2.

  2. X
    Gliosis at 16

    Fewer plaque-associated myeloid cells in APPPS1-21;Trem2+/R47H, compared with APPPS1-21 mice homozygous for wild-type Trem2.

Absent
  • Tangles at

    Tangles were not observed at 4 months of age, but hyperphosphorylated tau was detected in dystrophic neurites surrounding plaques.

  • Neuronal Loss at

    No differences in neuron number in cotical layer V in APPPS1-21;Trem2+/R47H mice relative to APPPS1-21 mice homozygous for wild-type Trem2, at 4 months of age.

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 TREM2 R47H, APP KM670/671NL (Swedish), PSEN1 L166P Trem2: Knock-In; APP: Transgenic; PSEN1: Transgenic Alzheimer's Disease

Reduction in the number and burden of fibrillar amyloid plaques in the hippocampus, fewer plaque-associated myeloid cells, and worse plaque-associated neuritic dystrophy, compared with APPPS1-21 mice homozygous for wild-type Trem2.

Unknown.

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