Researchers at the Korea Brain Research Institute in Daegu have found that cholesterol accumulation in Alzheimer’s disease may disrupt the flow of fluid that removes waste products from the brain. This effect could be associated with disease progression. The findings were published on the bioRxiv preprint server.
The team compared healthy genetically modified mice with animals engineered to model Alzheimer’s disease using five mutations. The researchers injected a dye into the cerebrospinal fluid and tracked how it moved through the brain.
In healthy mice, the dye entered the brain tissue and was gradually cleared. In mice with Alzheimer’s disease, it accumulated primarily around arteries and penetrated the tissue less effectively. The perivascular spaces — narrow channels along blood vessels through which fluid flows — were also significantly narrower than those in healthy animals.
The scientists also found that some of the dye accumulated in amyloid plaques, deposits of beta-amyloid protein characteristic of Alzheimer’s disease. The researchers believe these plaques may trap fluid and further impede its circulation.
A separate experiment pointed to a possible link between these disruptions and cholesterol. In healthy mice, the signal from a cholesterol-binding marker weakened over time. In the mice modeling Alzheimer’s disease, by contrast, the signal grew stronger throughout the two-hour observation period.
The authors suggest that cholesterol metabolism may be disrupted in Alzheimer’s disease, potentially interfering with fluid movement through the glymphatic system. Under normal conditions, this system helps remove metabolic waste from the brain, including proteins associated with Alzheimer’s disease.
However, it remains unclear whether cholesterol accumulation causes impaired brain clearance or whether cholesterol builds up as a result of disruptions that have already occurred.
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