A drug commonly used to prevent organ transplant rejection may offer an unexpected new approach to protecting people at increased risk of Alzheimer’s disease. Researchers at the University of Missouri have discovered that rapamycin, a medication also studied for its effects on aging, can improve blood flow in the brains of middle-aged adults who carry a gene variant linked to Alzheimer’s.
The findings could help scientists develop strategies to address Alzheimer’s risk long before memory problems appear. The research also adds to the University of Missouri’s growing contributions to understanding and potentially preventing the most common form of dementia.
The study was led by Ai-Ling Lin, a professor in the university’s School of Medicine and an investigator at the Roy Blunt NextGen Precision Health building. Her work focuses on identifying changes in the brain that occur before Alzheimer’s symptoms develop and finding ways to intervene early.
Why Brain Blood Flow Matters for Alzheimer’s Risk
A major focus of Lin’s research is the APOE4 gene variant, which is associated with a substantially increased risk of developing Alzheimer’s disease later in life.
People who carry APOE4 can experience reduced blood flow in certain areas of the brain years before they begin having noticeable memory difficulties. Because these circulation changes can occur so early, researchers believe they could provide an important warning sign of increased Alzheimer’s risk.
Lin’s latest findings suggest that improving brain circulation with an existing medication may be one way to address these early changes.
“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.”
An Anti-Aging Drug Shows Promise
Rapamycin is already used in medicine to prevent the immune system from rejecting transplanted organs and to treat certain rare conditions. However, researchers have also been investigating its potential to slow biological aging and protect the brain.
Before joining the University of Missouri, Lin conducted experiments involving mice that carried APOE4. Her earlier research showed that rapamycin could slow brain aging and increase blood flow in these animals.
Those results prompted an important question: Could rapamycin produce similar benefits in people who have a genetic predisposition to Alzheimer’s but have not yet developed the disease?
To investigate, Lin studied healthy adults between the ages of 45 and 65, including people who carried APOE4 and others who did not.
All participants received a low daily dose of rapamycin for four weeks. When researchers examined the results, they found a notable difference between the two groups.
Brain blood flow improved among participants carrying APOE4, but the same benefit was not observed in those without the gene variant. This suggests that rapamycin may have particular potential for people whose genetics place them at greater risk of Alzheimer’s.
Although the study did not establish whether the treatment could prevent Alzheimer’s or preserve memory over time, the improved circulation offers a promising direction for future research.
Women With the Alzheimer’s Risk Gene Saw the Greatest Benefits
Another intriguing finding emerged when the researchers examined differences between male and female participants.
Women carrying APOE4 experienced the largest improvements in brain blood flow following treatment. That result may be especially important because women account for nearly two-thirds of people living with 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.”
The results highlight the potential of precision medicine, an approach that considers individual characteristics, including genetics, when determining which treatments may be most effective.
Rather than assuming that a medication will benefit everyone equally, researchers hope to identify the people most likely to respond.
Moving Alzheimer’s Discoveries Toward Human Treatments
Lin, who is also a professor in the university’s College of Arts and Science, credits Mizzou’s collaborative research environment with helping advance discoveries like these.
At the Roy Blunt NextGen Precision Health building, scientists and medical professionals work together in the same facility. This collaboration is designed to help move promising laboratory findings into human clinical studies more quickly.
The latest results provide an encouraging starting point for investigating whether rapamycin could eventually help delay or reduce Alzheimer’s risk in genetically vulnerable individuals. More research will be needed to determine whether the changes in brain blood flow lead to lasting improvements in brain health or a lower likelihood of developing the disease.
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.