Rapamycin, an mTOR inhibitor with immunomodulatory properties, may mitigate AD pathology by restoring microglial functions.<h4>Methods</h4>Rapamycin was orally administered to 2-month-old 5xFAD and hAPP<sup>NL</sup>.<h4>Results</h4>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. This evidence concerns the gene MTOR and Alzheimer disease.