Is Cholesterol Behind Alzheimer’s?

By Emily Woodruff | May 14th, 2018

Here's how cholesterol may be a major player in not just brain health, but Alzheimer's disease.

Cholesterol is a word normally linked to heart disease. And we know eating fatty, greasy foods, like burgers, fries and butter can heighten your “bad” cholesterol and your chances of heart disease. But is cholesterol also a major player in brain health? Yes—according according to a recent study.

Cholesterol is a molecule made up of a waxy substance necessary to make hormones and vitamin D and help digest food. The human body makes cholesterol by itself, and it’s present in every cell in the body. But when you get too much cholesterol from fatty foods (think: butter, palm oil, coconut oil and full-fat dairy products), the molecules can group together and build up into plaques in your arteries. When too much plaque builds up, it can lead to higher chances of heart attack or stroke—both of which raise the risk of dementia.

But what about when cholesterol builds up in the brain? That’s what scientists at the University of Cambridge were studying when they found that cholesterol can trigger the build-up of beta-amyloid, the sticky protein that forms into plaques in the brains of Alzheimer’s patients. Beta-amyloid has long been thought of as the cause of Alzheimer’s, but scientists still aren’t sure how or why it forms. Beta-amyloid is typically present in very low levels in the brain, but in an Alzheimer’s brain, it begins to clump together.

“The levels of amyloid-beta normally found in the brain are about a thousand times lower than we require to observe it aggregating in the laboratory—so what happens in the brain to make it aggregate?” said Professor Michele Vendruscolo of Cambridge’s Centre for Misfolding Diseases, who led the research.

In the lab, the scientists saw that the presence of cholesterol encouraged beta-amyloid to stick together. Typically, beta-amyloid levels are so low in the brain that the molecules do not find each other to stick together, said the researchers. But beta-amyloid can attach to lipid molecules, which contain cholesterol, making it easier for the beta-amyloid molecules to find each other and attach. The researchers found that cholesterol speeds up the accumulation of beta-amyloid by 20 times.

The cholesterol found in the brain is not from a person’s diet—that cholesterol cannot pass through the blood-brain barrier. So what can be done to limit the impact of cholesterol on the build up of beta-amyloid?

“The question for us now is not how to eliminate cholesterol from the brain, but about how to control cholesterol’s role in Alzheimer’s disease through the regulation of its interaction with amyloid-beta,” said Vendruscolo. “We’re not saying that cholesterol is the only trigger for the aggregation process, but it’s certainly one of them.”

Cholesterol requires certain proteins to carry it around the brain, and those carriers regulate its levels in the brain. As we get older those proteins don’t function as well and, if cholesterol levels become off-balance then, the levels of beta-amyloid will be off, too. Researchers hope that identifying this chain effect in the brain might lead to a drug target for Alzheimer’s treatments.

“This work has helped us narrow down a specific question in the field of Alzheimer’s research,” said Vendruscolo. “We now need to understand in more detail how the balance of cholesterol is maintained in the brain in order to find ways to inactivate a trigger of amyloid-beta aggregation.”

This study was published in the journal Nature Chemistry.

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