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Alzheimer’s disease (AD) risk is significantly increased in carriers of the APOE4 allele, with early brain metabolic and vascular deficits preceding hallmark pathological changes. Rapamycin, an FDA-approved mTOR inhibitor, enhances mitochondrial function and synaptic activity, particularly in APOE4 mouse models, and improves brain vascular health and amyloid clearance. These findings position rapamycin as a promising preventive therapeutic for cognitively normal APOE4 carriers, emphasizing the need for genotype-tailored clinical trials.
