Research Models

Selected Results

2 Models

Name Other Names Strain Name Genetic Background Gene Mutation Modification Info Modification Disease Neuropathological
Phenotype
Cognition/ Behavior Other Phenotype Availability Primary Paper Visualization
Mouse Models (2)
APP NL-F/NL-F C57BL/6 APP APP KM670/671NL (Swedish), APP I716F Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and the Swedish and Beyreuther/Iberian mutations. APP: Knock-In Alzheimer's Disease Elevated Aβ peptides accumulating into plaques starting at 6 months. Microgliosis and astrocytosis, especially around plaques. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 18 months as measured by the Y maze. No significant impairment in the Morris water maze. No overexpression of APP. Generates wild-type levels of AICD. Available through Takaomi Saido. Saito et al., 2014 Yes
APP NL-G-F/NL-G-F C57BL/6 APP APP KM670/671NL (Swedish), APP I716F, APP E693G (Arctic) Knock-in of APP sequence including introns 15 to 17. Sequence was modified to contain a humanized Aβ region and three pathogenic mutations (Swedish, Beyreuther/Iberian, and Arctic). APP: Knock-In Alzheimer's Disease Aggressive amyloidosis with deposition in the cortex beginning at 2 months and approaching saturation by 7 months. Aβ deposition in heterozygous mice at 4 months. Subcortical amyloidosis. Exacerbated microgliosis and astrocytosis compared to APPNL-F mice. Reduced synaptophysin and PSD-95 indicative of synaptic loss. No tangle pathology or neurodegeneration. Memory impairment by 6 months as measured by the Y maze. No overexpression of APP. Wild-type levels of AICD. Available through Takaomi Saido. Saito et al., 2014 Yes

2 Visualizations

Phenotypes Examined

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

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

APP NL-F

Observed
  1. Plaques at 26

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

  2. Gliosis at 26

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

  3. Synaptic Loss at 39

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

  4. Cognitive Impairment at 78

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

Absent
  • Tangles at

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

  • Neuronal Loss at

    Absent.

Unknown
  • Changes in LTP/LTD at

    Unknown.

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

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

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

APP NL-G-F

Observed
  1. Plaques at 9

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

  2. Gliosis at 9

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

  3. Synaptic Loss at 17

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

  4. Cognitive Impairment at 26

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

Absent
  • Tangles at

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

  • Neuronal Loss at

    Absent.

Unknown
  • Changes in LTP/LTD at

    Unknown.

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

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

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