Landmark Study Links Brain Cholesterol to Alzheimer’s
Alzheimer’s disease is a form of dementia associated with the aberrant aggregation of the amyloid-β peptide. Although there is mounting evidence that implicates cholesterol in the pathogenesis of AD, a detailed mechanistic link is, however, lacking and remains to be fully established.
Now, a team led by researchers at the University of Cambridge, have discovered that brain cholesterol is a trigger for the formation of these notorious amyloid-beta clusters
. These in a toxic chain reaction eventually lead to the formation of amyloid plaques that result in the death of brain cells.“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.
The team examined what causes amyloid beta proteins to aggregate and found that cholesterol in lipid cell membranes that reside in the brain tend to trigger the accumulation of these proteins molecules.
The investigative team reported a vitro modeling experiment that showed aggregation of amyloid beta speeding up by a factor of 20 in the presence of cholesterol.
“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,” says Vendruscolo. “We’re not saying that cholesterol is the only trigger for the aggregation process, but it’s certainly one of them.”
“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.”
