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.
- Michele Vendruscolo
The international team, led by the University of Cambridge, have found that in the brain, cholesterol acts as a catalyst which triggers the formation of the toxic clusters of the amyloid-beta protein, which is a central player in the development of Alzheimer’s disease.
The results, published in the journal Nature Chemistry, represent another step towards a possible treatment for Alzheimer’s disease, which affects millions worldwide. The study’s identification of a new pathway in the brain where amyloid-beta sticks together, or aggregates, could represent a new target for potential therapeutics.
It is unclear if the results have any implications for dietary cholesterol, as cholesterol does not cross the blood-brain barrier. Other studies have also found an association between cholesterol and the condition, since some genes which process cholesterol in the brain have been associated with Alzheimer’s disease, but the mechanism behind this link is not known.
The Cambridge researchers found that cholesterol, which is one of the main components of cell walls in neurons, can trigger amyloid-beta molecules to aggregate. The aggregation of amyloid-beta eventually leads to the formation of amyloid plaques, in a toxic chain reaction that leads to the death of brain cells.
While the link between amyloid-beta and Alzheimer’s disease is well-established, what has baffled researchers to date is how amyloid-beta starts to aggregate in the brain, as it is typically present at very low levels.
“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.
Using a kinetic approach developed over the last decade by the Cambridge team and their collaborators at Lund University in Sweden, the researchers found in in vitro studies that the presence of cholesterol in cell membranes can act as a trigger for the aggregation of amyloid-beta.
Image: Mouse model of Alzheimer's disease
Credit: NIH Image Gallery
Reproduced courtesy of the University of Cambridge