Research Models
APP23
Synonyms: B6-Tg/Thy1APP23Sdz
Species: Mouse
Genes: APP
Modification: APP: Transgenic
Disease Relevance: Alzheimer's Disease, Cerebral Amyloid Angiopathy
Strain Name: B6.Cg-Tg(Thy1-APP)3Somm/J
Summary
Phenotype Characterization
When visualized, these models will distributed over a 18 month timeline demarcated at the following intervals: 1mo, 3mo, 6mo, 9mo, 12mo, 15mo, 18mo+.
Absent
- Tangles
- Synaptic Loss
- Changes in LTP/LTD
No Data
Plaques
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).
Tangles
Dystrophic neurites containing hyperphopshorylated tau surounds Aβ plaques, but no neurofibrillary tangles are observed (Sturchler-Pierrat et al., 1997).
Synaptic Loss
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).
Neuronal Loss
Neuronal loss (14-28%) has been reported in the CA1 region of the hippocampus in 14-18 month old mice (Calhoun et al., 1998).
Gliosis
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).
Changes in LTP/LTD
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).
Cognitive Impairment
Spatial memory defects in Morris Water maze at 3 months and progresses with age (Van dam et al., 2003; Kelly et al., 2003).
Last Updated: 25 Nov 2019
Further Reading
No Available Further Reading
COMMENTS / QUESTIONS
Mount Sinai School of Medicine, NYU
If the claim of this paper on the induction of tau pathology by APP mutations is replicated, these mice will be the best available AD model.
View all comments by Nikolaos K. RobakisOsaka City University Medical School
There are some transgenic mice to show amyloid plaques but this is the first study to show the presence of tau alteration to suggest the occurrence of PHF.
View all comments by Hiroshi MoriMake a comment or submit a question
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