Cholesterol drives Alzheimer’s plaque formation

Scientists from the University of Virginia School of Medicine and their collaborators found that cholesterol produced by cells called astrocytes is required for controlling the production of amyloid beta, a sticky protein that builds up in the brains of patients with Alzheimer’s. The protein accumulates into insoluble plaques that are a hallmark of the disease. Many efforts have targeted these plaques in the hope that removing or preventing them could treat or prevent Alzheimer’s. The findings, published in the scientific journal PNAS, offer important insights into how and why the plaques form and may explain why genes associated with cholesterol have been linked to increased risk for Alzheimer’s. The results also provide scientists with important direction as they seek to prevent Alzheimer’s. “This study helps us to understand why genes linked to cholesterol are so important to the development of Alzheimer’s disease,” said researcher Dr. Heather A. Ferris of UVA Health’s Division of Endocrinology and Metabolism. “Our data point to the importance of focusing on the production of cholesterol in astrocytes and the transport to neurons as a way to reduce amyloid beta and prevent plaques from ever being formed.”

While cholesterol is often associated with clogged arteries and heart disease, it plays important roles in the healthy body. The body makes cholesterol naturally so it can produce hormones and carry out other important functions. The new discovery from Ferris and her collaborators adds a new entry to cholesterol’s list of responsibilities.

The scientists found that astrocytes help drive the progression of Alzheimer’s by making and distributing cholesterol to brain cells called neurons. This cholesterol buildup increases amyloid beta production and, in turn, fuels plaque accumulation.  Normally, cholesterol is kept quite low in neurons, limiting the buildup of amyloid beta. But in Alzheimer’s, the neurons lose their ability to regulate amyloid beta, and the result is plaque formation. Blocking the astrocytes’ cholesterol manufacturing “robustly” decreased amyloid beta production in lab mice, the researchers report in a new scientific paper. It’s too soon to say if this could be mimicked in people to prevent plaque formation, but the researchers believe that further research is likely to yield important insights that will benefit the battle against Alzheimer’s. Additional research into the discovery could shed light on how to prevent the over-production of amyloid beta as a strategy against Alzheimer’s, the researchers believe. 

Source: University of Virginia news release