Washington, Jan 18 : A study by researchers at the Washington University School of Medicine in St. Louis has found that altering the brain's lipid metabolism may help reduce Alzheimer's plaques.
The study, conducted on a mouse model, has already shown positive results in the rodents, and highlights a new possibility for potential treatment of the disease.
The study was led by David M. Holtzman, M.D., the Andrew and Gretchen Jones Professor and chair of the Department of Neurology at the School of Medicine and neurologist-in-chief at Barnes-Jewish Hospital, who said that elevated levels of the protein ABCA1 considerably reduced buildup of brain plaques that are characteristic of Alzheimer's disease.
"It's becoming clear that ABCA1 may be a good drug target for Alzheimer's therapies. There are known drugs that can increase ABCA1 levels, and with some further development of this or similar classes of drugs and additional insights into how ABCA1 slows down plaque deposition, there may be a way to create a new approach to Alzheimer's treatment," said Holtzman.
ABCA1 was discovered in 2001 and is a naturally occurring enzyme already under study for its potential to treat heart disease. Lipids like cholesterol are insoluble, so to be transported through the bloodstream and into and out of cells and organs, they have to combine with molecules known as apolipoproteins. This process known as lipidation, is facilitated by ABCA1.
A primary risk factor for Alzheimer's disease is an apolipoprotein known as apoE. Variants of apoE are linked to major changes in an individual's risk of developing late-onset Alzheimer's disease.
It was revealed in an earlier research that ABCA1 also lipidates good cholesterol in the brain. When the researchers utilized mice lacking the gene for ABCA1 and bred them to mouse model of Alzheimer's disease, the animals developed a much great number of the brain plaques that are characteristic of the disease.
In the new experiment, the scientists created a line of mice genetically altered to make unusually high levels of ABCA1 in the brain. When that line was crossbred with their Alzheimer's disease mouse model, it was found that mice with high ABCA1 levels built up plaques in their brains much more slowly and to a much lesser extent than those with normal ABCA1 levels.
This demonstrated that ABCA1 is facilitating the lipidation of HDL and apoE. According to Holtzman, this allows apoE to better hunt amyloid beta, the main ingredient of plaques, from the brain in a way that decreases the chances that plaques will begin to form.
A class of drugs is already available that increases ABCA1 levels: LXR (liver X receptor) agonists.
However, Holtzman indicated that these drugs need to be fine-tuned to avoid an undesirable side effect that increases fat buildup in the liver.
The study is appearing this month in The Journal of Clinical Investigation.