Researchers at Washington University School of Medicine in St. Louis have uncovered a significant connection between Alzheimer’s disease and cholesterol.
They found that in mice, Alzheimer’s-like tau deposits in the brain lead to a buildup of a specific type of cholesterol, known as cholesteryl esters. This buildup is linked to brain damage and behavioral changes associated with Alzheimer’s.
The Role of Cholesteryl Esters
The study, published in Neuron, explains that cholesteryl esters accumulate in areas of the brain where tau proteins are over-accumulated. This leads to brain cell damage and death.
The research team, led by Dr. David M. Holtzman, discovered that reducing the levels of cholesteryl esters could prevent this damage, suggesting new therapeutic possibilities.
The researchers used mice with a high-risk gene for tau accumulation, which causes neurodegeneration. These mice also carried a modified human APOE gene—either APOE3, which poses average Alzheimer’s risk, or APOE4, which increases the risk.
They found that APOE4 is associated with distorted lipid metabolism in the brain, resulting in microglia (immune cells) filled with cholesteryl esters.
Potential Therapeutic Implications
To test potential treatments, the researchers used an experimental drug called GW3965, which lowers lipid levels in cells.
Treated mice showed significantly more brain volume retention, lower tau levels, and less inflammation compared to untreated mice. This indicates that targeting lipid metabolism could be an effective strategy in combating Alzheimer’s disease.
One major challenge is that current drugs, like GW3965, can cause fatty liver disease due to their effects on liver lipid metabolism.
Researchers are working to develop drugs that can reduce cholesteryl esters in the brain without these side effects. If successful, these drugs could benefit not only Alzheimer’s patients but also those with heart disease.
This study marks a significant step in understanding and potentially treating Alzheimer’s disease. By focusing on the role of cholesteryl esters in brain damage, researchers are opening new avenues for preventing and treating this debilitating condition.
If you care about dementia, please read studies about Early heart rhythm problem linked to higher dementia risk and findings of Green leafy vegetables may help reduce Alzheimer’s risk.
For more information about Alzheimer’s disease, please see recent studies about Foods that reduce Alzheimer’s risk and results showing that Scientists link dietary antioxidants to Alzheimer’s prevention.
The research findings can be found in
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