A new study from the University of Missouri offers hope for those who are at significantly higher risk of developing Alzheimer’s disease later in life, further establishing Mizzou as a leader in research on the most common cause of dementia.

Ai-Ling Lin, a professor in the School of Medicine and investigator at the Roy Blunt NextGen Precision Health building, is working to identify ways to prevent the onset of the disease.

Her research focuses on people who carry the APOE4 gene variant, which is associated with a higher risk of Alzheimer’s disease. These individuals often experience reduced blood flow to certain regions of the brain years before memory problems emerge, making diminished cerebral blood flow a potential early indicator of Alzheimer’s risk.

In her latest study, Lin found that an anti-aging drug increased blood flow to the brains of healthy middle-aged adults who carry the APOE4 gene.

“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.”

Before coming to Mizzou, Lin studied the drug rapamycin, which is typically prescribed to prevent organ transplant rejection and to treat certain rare diseases. Lin showed that the drug can also slow down brain aging and improve brain blood flow for mice with APOE4.

For the recent study, Lin wanted to determine whether the same benefits would extend to people ages 45 to 65 who carry the APOE4 gene but have not yet developed symptoms of Alzheimer’s disease.

Participants with and without the gene variant took a low dose of rapamycin daily for four weeks. Lin found that only those with APOE4 showed improved blood flow in the brain, suggesting the drug could help preserve cognitive function for those at higher risk of developing Alzheimer’s disease.

“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,” she said. “This research is an example of precision medicine, as we work to identify who can benefit from this drug the most.”

Lin, also a professor of biological sciences in the College of Arts and Science, said Mizzou provides an ideal environment for this work. The Roy Blunt NextGen Precision Health building brings researchers and clinicians together under one roof, helping accelerate the translation of discoveries from the laboratory to human clinical trials.

The study, “EXPRESS: Rapamycin increases cerebral blood flow and modulates metabolic, inflammatory, and microbiome profiles in healthy middle-aged APOE4 carriers: a pilot single-arm trial" was published in Journal of Cerebral Blood Flow & Metabolism.