We're all too familiar with the devastating consequences of Alzheimer's disease, but scientists are still working to figure out how it starts in the brain. A new study is pointing the finger at one suspect in particular: brain cholesterol.
Based on in vitro modelling in the lab, cholesterol was shown to speed up the aggregation of amyloid beta (Aβ) molecules by a factor of 20. This build-up of amyloid beta proteins is thought to be crucial in the way Alzheimer's destroys cells in the brain.
While other studies have linked higher cholesterol with a higher risk of Alzheimer's before, this dramatic new evidence shows for the first time how cholesterol molecules can act as a catalyst in causing amyloid beta to cluster into plaques.
"We're not saying that cholesterol is the only trigger for the aggregation process, but it's certainly one of them," says lead researcher Michele Vendruscolo, from the University of Cambridge in the UK.
You're probably most familiar with cholesterol as something we need to limit in our diets if we want to stay healthy, but a quarter of the cholesterol in our bodies is found in the brain.
What's more, cholesterol can't cross the blood-brain barrier – the brain makes its own allocation by itself. That means having a high level of cholesterol in your blood, which is associated with various cardiovascular diseases, isn't necessarily linked to having a high level of cholesterol in the brain.
And to complicate matters further, cholesterol is actually very important to the way the brain functions. We can't just get rid of it.
What the researchers observed was amyloid beta molecules sticking to the lipid cell membranes that contained cholesterol, giving the molecules a way to clump together and to start aggregating.
That would help explain why amyloid beta – usually present in very low levels in the brain – can suddenly start ganging up on healthy neurons to kickstart Alzheimer's.
But because cholesterol plays a vital role in the normal functioning of cells, it's not a good idea to try and reduce the concentration of cholesterol in the brain. Another approach is going to be needed if this turns into a treatment option.
"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.
For a number of years scientists have been looking at the relationship between cholesterol in the brain and cognitive function, but the results so far have been inconsistent and inconclusive. Now researchers have got more data for the puzzle.
Cholesterol requires specific protein carriers to ferry it around the brain, and as we get older, these carriers become less effective – the chemical imbalance that causes could be one area for future research.
The latest statistics show 47 million people currently living with Alzheimer's across the world, and with that figure expected to rise sharply in the future, the race is on to try and understand more about how Alzheimer's takes hold – and how it can be stopped.
"This work has helped us narrow down a specific question in the field of Alzheimer's research," says 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."
The research has been published in Nature Chemistry.