The blood-brain barrier is impermeable to cholesterol, yet high blood cholesterol is associated with increased risk of Alzheimer’s disease and vascular dementia. However, the underlying mechanisms mediating this relationship are poorly understood.
A study published in the open-access journal PLOS Medicine by Vijay Varma and colleagues at the National Institute on Aging, part of the National Institutes of Health, in Baltimore, Maryland, suggests that disturbances in the conversion of cholesterol to bile acids (called cholesterol catabolism) may play a role in the development of dementia.
“To further extend these findings, we are now testing whether approved drugs for other diseases that may correct bile acid signaling abnormalities in the brain could be novel treatments for Alzheimer’s disease and related dementias,” said senior author Madhav Thambisetty, M.D., Ph.D., investigator and chief of the Unit of Clinical and Translational Neuroscience in the NIA’s Laboratory of Behavioral Neuroscience. “These analyses are being pursued in the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study.”
Little is known about how high blood cholesterol may lead to an increased risk of Alzheimer’s and dementia yet understanding the underlying processes may lay the foundation for discovering effective therapeutics.
To investigate whether abnormalities in cholesterol catabolism through its conversion to bile acids is associated with development of dementia, researchers drew on more than 1800 participants from two prospective studies: the Baltimore Longitudinal Study of Aging (BLSA) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI).