A new study, led by researchers at the University of Cambridge in the United Kingdom, concludes that cholesterol may play a significant role in the development of Alzheimer’s disease.
Cholesterol is a waxy substance that can build up on the walls of arteries, potentially causing health problems.
Approximately 71 million people in the United States live with high levels of low-density lipoprotein (LDL), or “bad cholesterol.”
A new study, published in the journal Nature Chemistry, suggests that this cholesterol could also act as a catalyst for clusters of a protein called amyloid-beta to form in the brain.
Amyloid-beta is well known to be a key contributing factor to Alzheimer’s disease, which currently affects around 5.4 million people in the U.S. When amyloid-beta aggregates, it forms into plaques that are toxic to brain function and kills off brain cells.
However, scientists have struggled to identify how the clusters of amyloid-beta form in the first place.
What scientists do know is that amyloid-beta molecules do not normally stick together in the brain because they are only present in low levels, and they are spread out across the brain.
The Cambridge team joined forces with researchers at Lund University in Sweden to investigate how amyloid-beta manages to form into clusters in Alzheimer’s disease.
They revealed that amyloid-beta can stick to lipids, a type of insoluble molecule that includes fats, steroids, phospholipids, and waxes. In particular, amyloid-beta was found to stick very well to lipid cell membranes containing cholesterol.
Then, once amyloid-beta molecules become stuck to cholesterol-containing lipid cell membranes in the vicinity of other “stuck” amyloid-beta molecules, there is a greater chance that these molecules will encounter each other, causing clusters to begin forming.
The team calculates that the presence of cholesterol caused amyloid-beta clusters to develop 20 times faster than they would have otherwise.
Earlier studies have mapped a link between cholesterol and Alzheimer’s; for instance, scientists know that some of the same genes that process cholesterol in the brain are also implicated in Alzheimer’s. However, it is unclear how they are linked.
The authors of the recent study are not sure if dietary cholesterol plays a role in Alzheimer’s, as this kind of cholesterol does not cross into the brain from the bloodstream.
So, although it is generally good for your health to eat a balanced diet without too much cholesterol, how much cholesterol you consume in your diet is not thought to be an issue in regards to your risk of developing Alzheimer’s.
In fact, study co-author Prof. Michele Vendruscolo — of the Centre for Misfolding Diseases at the University of Cambridge — says that it is not the cholesterol in itself that is the problem.
“The question for us now,” he says, “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. We’re not saying that cholesterol is the only trigger for the aggregation process, but it’s certainly one of them.”
Prof. Vendruscolo explains that cholesterol is moved around the body by dedicated “protein carriers” such as ApoE, which, in its mutated form, has also been studied as a risk factor for Alzheimer’s.
In older people, protein carriers are less effective, interrupting the movement of cholesterol around the body. So, it may be possible for scientists in the future to design drugs that target this process, helping to control the balance of cholesterol and amyloid-beta in the brain.
“This work has helped us narrow down a specific question in the field of Alzheimer’s research,” concludes Prof. 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.”