Cerebellar Resistance to Amyloid Plaque Deposition and Elevated Microglial ECM Proteoglycan Uptake in 5xFAD Mice.

ABSTRACT: In both Alzheimer's disease (AD) patients and animal models, senile plaques are generally observed in the cerebral cortex rather than the cerebellum. The mechanisms underlying the regional resistance of the cerebellum to amyloid plaque deposition remain poorly understood. We investigated this cerebellar resistance using 5xFAD mice, an amyloidosis model with high expression of mutant human APP and PSEN1 in the cortex and cerebellum. In aged 5xFAD mice, the cerebellum had minimal amyloid-β (Aβ) deposition despite robust transgene expression, correlating with lower expression levels of IBA1, CD68, TREM2, and CD36 (although elevated expression of CD45 and MHC I) compared to the cortex. Consistent with the absence of plaques, cerebellar tissue lacked the dystrophic VGLUT1-positive

SUBMITTER: Cangalaya C 

PROVIDER: S-EPMC12839178 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature