Changes in the degradation of cholesterol in the body can accelerate the progression of dementia

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Researchers at the National Institute on Aging, part of the National Institutes of Health, are looking for candidates for drugs that can correct brain metabolic abnormalities, such as cholesterol breakdown. Credit: Dr. Vijay R. Varma

The blood-brain barrier is impermeable to cholesterol, but high cholesterol is associated with an increased risk of Alzheimer’s disease and vascular dementia. However, the underlying mechanisms involved in this relationship are little known. A study published in the open access journal PLOS medicine by Vijay Varma and colleagues at the National Institute on Aging, which is part of the National Institutes of Health in Baltimore, Maryland, suggests that alterations in the conversion of cholesterol to bile acids (called cholesterol catabolism) may play a role in the development of dementia.

Little is known about how can cause an increased risk of Alzheimer’s and , however, understanding the underlying processes can lay the groundwork for discovering effective therapeutics. Investigate if there are any anomalies in catabolism by converting it to is associated with the development of dementia, the researchers looked at more than 1,800 participants from two prospective studies: the Baltimore Longitudinal Study of Aging (BLSA) and the Alzheimer’s Disease Neuroimaging Initiative (DNA) ).

First, the research team investigated whether cholesterol catabolism was associated with typical Alzheimer’s brain abnormalities and . They then tested whether exposure to anti-cholesterol drugs that block the absorption of bile acids into the bloodstream was associated with an increased risk of dementia among more than 26,000 patients in general medicine clinics in the UK. Finally, they examined 29 BLSA autopsy samples to determine if people with Alzheimer’s disease usually have altered levels of bile acids in their brain.

The authors found that the risk of vascular dementia increased for men, but not for women, with more prescriptions for drugs that block bile acid. Their findings suggest that cholesterol catabolism and bile acid synthesis may affect the progression of dementia through sex-specific effects in brain signaling pathways. However, additional studies are needed, as research was limited by the relatively small number of autopsy samples. In addition, experimental studies are required to better understand the role of cholesterol degradation in dementia.

“To further expand these findings, we are now testing whether drugs approved for other diseases that can correct bile acid signaling abnormalities in the brain could be new treatments for Alzheimer’s disease and related dementias,” he said. ‘author, MD, Ph.D. ., researcher and head of the Clinical and Translational Neuroscience Unit at the Behavioral Neuroscience Laboratory of the NIA. “These analyzes are being conducted in the study of Drug Reuse for Effective Alzheimer’s Drugs (DREAM).”


Changes in white matter in the brain are found in frontotemporal dementia


More information:
Varma VR, Wang Y, An Y, Varma S, Bilgel M, Doshi J, et al. (2021) Synthesis, modulation and dementia of bile acids: metabolomic, transcriptomic and pharmacoepidemiological study. PLoS Med 18 (5): e1003615. doi.org/10.1371/journal.pmed.1003615

Citation: Changes in Cholesterol Degradation in the Body May Accelerate the Progression of Dementia (2021, May 27) Retrieved May 27, 2021 at https://medicalxpress.com/news/2021-05-cholesterol-body- dementia.html

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