Study published in JCI suggests that ABCA1 allows apoE to bind better to amyloid beta, decreasing chances of plaque build-up.
Increasing levels of a protein that helps the brain use cholesterol may slow the development of Alzheimer’s disease changes in the brain, according to researchers.
Discovered in 2001, ABCA1 is a naturally occurring enzyme already under study for its potential to treat heart disease. ABCA1 is known to facilitate lipidation.
In the current study, the scientists created a line of mice genetically altered to make unusually high levels of ABCA1 in the brain. When they crossbred that line with an Alzheimer’s disease mouse model, they found mice with high ABCA1 levels built up plaques in their brains more slowly and to a lesser extent than those with normal ABCA1 levels.
The work showed that ABCA1 is facilitating the lipidation of HDL and apoE. An earlier experiment by other scientists showed that lipidated apoE binds more tightly to soluble amyloid beta than non-lipidated apoE. Senior author David M. Holtzman, M.D., chair of the Department of Neurology at the Washington University School of Medicine theorizes that this allows apoE to better scavenge amyloid beta, the main ingredient of plaques, from the brain in a way that decreases the chances that plaques will begin to form.
The research was performed by investigators at Washington University School of Medicine, University of British Columbia, and Eli Lilly. The study appears online in the Journal of Clinical Investigation.
