A transplant drug improved brain blood flow in a four-week study of healthy adults at higher genetic risk of Alzheimer’s, suggesting a possible role in prevention.
Blood flow to parts of the brain can drop years before memory problems appear in people who carry APOE4, a gene variant associated with a higher risk of Alzheimer’s disease. That change offers a possible early warning, but researchers still need to determine whether intervening during those symptom-free years can help prevent the disease from developing.
Ai-Ling Lin, a professor in the University of Missouri’s School of Medicine, investigated that possibility using rapamycin, a drug being studied for its anti-aging effects. Healthy adults ages 45 to 65, including people with and without APOE4, took a low dose daily for four weeks. None had developed symptoms of Alzheimer’s disease, and only those carrying the variant showed improved blood flow in the brain.
“We also found that females with APOE4 saw the greatest improvement in brain blood flow, which is significant given that nearly two-thirds of people with Alzheimer’s are women,” Lin said. “This research is an example of precision medicine, as we work to identify who can benefit from this drug the most.”
Rapamycin slowed brain aging in mice
Lin had begun exploring rapamycin before coming to Missouri, looking beyond its usual roles in preventing organ transplant rejection and treating certain rare diseases. In mice with APOE4, she found that it could slow brain aging as well as improve cerebral blood flow. Those findings prompted her to investigate whether the benefits would extend to middle-aged people carrying the same variant.
Improved blood flow in these healthy adults suggests a possible role for rapamycin in preserving cognitive function, although the four-week study does not establish whether it will protect memory or prevent Alzheimer’s later in life. “Alzheimer’s tends to happen more in older people, especially for those with APOE4,” Lin said. “If we can slow down aging in the brain for those people most at risk, maybe we can reduce the risk of them developing Alzheimer’s disease.”
Reference: “EXPRESS: Rapamycin increases cerebral blood flow and modulates metabolic, inflammatory, and microbiome profiles in healthy middle-aged APOE4 carriers: a pilot single-arm trial” by Chetan Aware, Caitlin Maria Neher, Carter Woods, Oleksandr Khegai, Alok Kumar Dwivedi, Maalavika Govindarajan, Kira Ivanich, Mehmet Kurt, David Beversdorf, Jianlin Cheng, Nathan Bresette, Taixing Cui, Priti Balchandani, Mitzi M. Gonzales, Aaron C Ericsson, Talissa Altes and Ai-Ling Lin, 10 September 2026, Journal of Cerebral Blood Flow & Metabolism.
DOI: 10.1177/0271678X261490342
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