Rapamycin, a drug commonly used to prevent organ-transplant rejection, may offer a way to address early brain changes linked to Alzheimer’s disease. In a University of Missouri pilot study, four weeks of low-dose rapamycin improved cerebral blood flow in healthy middle-aged adults carrying the APOE4 gene variant, which is associated with a higher risk of developing Alzheimer’s later in life. The strongest improvement was observed among women with APOE4.
The findings could help researchers develop strategies to address Alzheimer’s risk before memory problems appear. They also add to the University of Missouri’s research into the causes and potential prevention of common forms of dementia.
Why cerebral blood flow matters in Alzheimer’s risk
The study was led by Ai-Ling Lin, a professor of medicine at the University of Missouri and a researcher at the Roy Blunt NextGen Precision Health building. Lin studies brain changes that occur before Alzheimer’s symptoms develop and looks for ways to intervene early.
Her research focuses in part on APOE4, a gene variant associated with a significantly increased risk of developing Alzheimer’s disease later in life. People who carry APOE4 may experience reduced blood flow in some brain regions years before substantial memory loss begins.
Because these circulatory changes can occur early, they may serve as warning signs of increased Alzheimer’s risk. Lin’s latest findings suggest that existing drugs capable of improving cerebral circulation could offer one way to address those changes.
“Alzheimer’s disease tends to occur more frequently in older people, especially those with APOE4,” Lin says. “If we can slow brain aging in those most at risk, we may be able to reduce their risk of developing Alzheimer’s disease.”
Testing rapamycin in people with APOE4
Rapamycin is used to prevent the immune system from rejecting transplanted organs and to treat certain rare conditions. Researchers are also studying the drug for its potential to slow biological aging and protect the brain.
Before joining the University of Missouri, Lin conducted experiments in mice carrying APOE4. That research indicated that rapamycin could slow brain aging and increase blood flow in the animals.
Those results raised the question of whether rapamycin could produce a similar effect in people with a genetic predisposition to Alzheimer’s disease who had not developed the disease.
To investigate, Lin studied healthy adults between 45 and 65 years old, including participants who carried APOE4 and participants who did not. All participants received a low daily dose of rapamycin for four weeks.
After treatment, cerebral blood flow had improved in participants carrying APOE4. Researchers did not observe a similar effect in participants without the variant. The result suggests that rapamycin may have particular potential for people at genetically elevated risk of Alzheimer’s disease.
However, the study does not establish whether rapamycin can prevent Alzheimer’s disease or preserve memory over the long term. The improvement in cerebral blood flow provides a direction for further research, rather than proof of a clinical benefit.
Women with APOE4 showed the greatest improvement
The researchers also examined differences between male and female participants. Women carrying APOE4 experienced the largest improvement in cerebral blood flow after treatment.
The finding is notable because women account for nearly two-thirds of people with Alzheimer’s disease.
“We also found that women with APOE4 had the greatest improvement in cerebral blood flow, which is important given that nearly two-thirds of Alzheimer’s patients are women,” Lin said. “This study is an example of precision medicine, working to identify who can benefit most from this drug.”
Precision medicine considers individual characteristics, including genetics, when determining which treatments may be most effective. Rather than assuming that a drug will benefit everyone equally, researchers aim to identify the people most likely to respond.
Next steps for Alzheimer’s research
Lin, who is also a professor in the university’s College of Arts and Sciences, credited Mizzou’s collaborative research environment with helping advance the work.
At the Roy Blunt NextGen Precision Health building, scientists and medical professionals work together in the same facility. The collaboration is intended to help translate promising clinical test results into human clinical studies more quickly.
The results provide an encouraging starting point for investigating whether rapamycin can ultimately delay or reduce Alzheimer’s risk in people who are genetically vulnerable. Further research will be needed to determine whether changes in cerebral blood flow lead to lasting improvements in brain health or reduce the likelihood of developing the disease.
The study, “Express: Rapamycin increases cerebral blood flow and modulates metabolism, inflammation, and microbiome profiles in healthy middle-aged APOE4 carriers: a pilot single-arm study,” was published in the Journal of Cerebral Blood Flow and Metabolism.
Source: www.sciencedaily.com
