First, the research team investigated whether cholesterol catabolism was associated with brain abnormalities typical of Alzheimer’s and vascular dementia. They next tested whether exposure to cholesterol medications that block bile acid absorption into the bloodstream was associated with an increased risk of dementia among more than 26,000 patients from general practice clinics in the United Kingdom.
‘Changes in how cholesterol breaks down in the body may accelerate the progression of dementia. This suggests that some cholesterol medications may impact signaling pathways in the brain, particularly in men.
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Finally, they examined 29 autopsy samples from the BLSA to determine whether people with Alzheimer’s disease tend to have altered levels of bile acids in their brains. The authors found that the risk of vascular dementia increased for males, but not females, with a greater number of prescriptions of bile acid blocking drugs.
Their findings suggest that cholesterol catabolism and bile acid synthesis may impact dementia progression through sex-specific effects on brain signaling pathways. However, additional studies are needed as the research was limited by the relatively small numbers of autopsy samples. In addition, experimental studies are required to better understand the role of cholesterol breakdown in 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.”
Source: Medindia
