Researchers discover cholesterol drug’s potential as treatment for Alzheimer’s, other dementia
Researchers from the University of Arkansas for Medical Sciences (UAMS) have discovered that an FDA-approved cholesterol drug holds the potential to disrupt the progression of Alzheimer's disease and other forms of dementia.
The research team published its findings in the journal Aging Biology. Akshatha Ganne, a postdoctoral fellow in the UAMS College of Medicine’s Department of Geriatrics, is the lead author. Srinivas Ayyadevara, Ph.D., associate professor in the College of Medicine, and Robert J. Shmookler Reis, Ph.D., professor in the College of Medicine, are the corresponding/senior authors of the paper.
Approved by the U.S. Food and Drug Administration (FDA) in 2002, ezetimibe is a prescription medication that reduces the amount of cholesterol absorbed by the intestines.
The team’s research focused on aggregates made up of tangled proteins, commonly seen in the brains of Alzheimer’s patients. Scientists consider these and similar accumulations to be key factors in the progression of most or all cognitive disorders, Reis said.
He added, “We found that they also occur in brains of those with heart disease, which is known to increase the subsequent risk of Alzheimer’s disease.”
The researchers used 3D-analysis tools to map the sticky sites within typical aggregates and to discover which ones are most important for holding these clumps together. This computer analysis was conducted by Meenakshisundaram Balasubramaniam, Ph.D., assistant professor in the Department of Geriatrics, who then simulated interactions with more than 1,800 FDA-approved medications, to seek molecules that best disrupt the aggregation process. That search led them to ezetimibe, which was then shown to prevent specific aggregate proteins from sticking to one another in lab-grown neurons.
To assess the drug’s real-world effect, the team explored a clinical database to analyze data on approximately 950,000 older adults — 4,361 of whom were receiving ezetimibe to lower cholesterol levels. The data revealed that patients taking ezetimibe had a much lower incidence of Alzheimer’s and related forms of dementia than those in the control group, according to Joseph Asante, Ph.D., one of the study co-authors.
