Rapamycin Boosts Brain Blood Flow in APOE4 Carriers, Strongest Effect in Women

The team gave 45-65-year-old volunteers without dementia a low daily rapamycin dose for four weeks and measured regional cerebral blood flow with MRI. APOE4 carriers showed improved perfusion in areas typically hypoperfused years before cognitive symptoms, while non-carriers showed no change. This matches earlier mouse data from the same lab showing rapamycin slowed brain aging in APOE4 models via mTOR inhibition and vascular effects. The sex difference is clinically relevant because women comprise nearly two-thirds of Alzheimer's cases and female APOE4 carriers had the largest perfusion gains. The design was a small, short-term, open-label pilot without a placebo arm or cognitive endpoints, limiting causal claims about dementia prevention. Future work needs placebo-controlled trials of at least one year with PET amyloid/tau imaging and longitudinal cognitive testing to test whether perfusion gains translate into delayed onset. Larger samples stratified by sex and APOE genotype would strengthen precision-medicine claims.