Generation and Characterization of the First Murine Model of Alzheimer's Disease with Mutated AβPP Inserted in a BALB/c Background (C.B6/J-APPswe)

第一个在 BALB/c 背景下植入突变 AβPP 的阿尔茨海默病小鼠模型 (C.B6/J-APPswe) 的生成和表征

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Background

Numerous mouse models of Alzheimer's disease (AD) are available, but all suffer from certain limitations, thus prompting further attempts. To date, no one model exists with amyloidopathy in a BALB/c strain.

Conclusion

C.B6/J-APPswe mice develop most of the distinctive features of AD and is a suitable model for the study of brain atrophy mechanisms and of the differences between males and females in the onset of cognitive/non-cognitive deficits.

Methods

We analyzed five groups at different ages (3, 6, 9, 12, and 16-18 months) of C.B6/J-APPswe and wild-type mice (50% males and 50% females) for the main hallmarks of AD by western blotting, amyloid-β (Aβ) ELISA, immunocytochemistry, electrophysiology, and behavioral tests.

Objective

To generate and characterize the C.B6/J-APPswe mouse, a model of AD with a mutated human gene for the amyloid-β protein precursor (AβPP) inserted in a BALB/c background.

Results

The C.B6/J-APPswe mouse displays early AβPP and Aβ production, late amyloid plaques formation, high level of Tau phosphorylation, synaptic deficits (reduced density and functional impairment due to a reduced post-synaptic responsiveness), neurodegeneration caused by apoptosis and necroptosis/necrosis, microgliosis, astrocytic abnormalities, and sex-related differences in explorative behavior, anxiety-like behavior, and spatial long-term and working memories. Social housing is feasible despite the intra-cage aggressiveness of male animals.

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