Rapamycin Reduces Amyloid-β Plaques and Improves Behavioral Performance in a Sex-Dependent Manner in Mouse Models of Amyloidosis.

ABSTRACT:

Background

Alzheimer's disease (AD), the most common form of dementia, lacks effective disease-modifying treatments. Rapamycin, an mTOR inhibitor with immunomodulatory properties, may mitigate AD pathology by restoring microglial functions.

Methods

Rapamycin was orally administered to 2-month-old 5xFAD and hAPP^NL.

Results

Rapamycin treatment reduced the cerebral Aβ plaque burden, alleviated dystrophic neurites, suppressed glial hyperactivation, and increased plaque-associated microglial density in both mouse models, with more pronounced effects in female mice. These pathological improvements were associated with attenuated deficits in hippocampal-dependent memory tasks (spontaneous alternation in the Y-maze and contextual fear conditioning tasks). Mechanist

SUBMITTER: Guo S 

PROVIDER: S-EPMC12945924 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature