Potential New Target Found for Alzheimer's Disease
In study on mice, researchers were able to limit effects on brain
WEDNESDAY, Dec. 9, 2009 (HealthDay News) -- The low-density lipoprotein receptor may help reduce brain damage caused by Alzheimer's disease, a new study suggests.
Accumulation of amyloid beta-protein (A-beta) plaques in the brain plays a major role in Alzheimer's, and previous research has implicated apolipoprotein E (apoE) in the accumulation of A-beta plaques, according to background information in the study, published in the Dec. 10 issue of Neuron.
"Modulating the function of proteins that control apoE metabolism in the brain will likely alter the extent of amyloid deposition and ultimately affect the disease process," Dr. David M. Holtzman, of the Washington University School of Medicine, said in a news release from the journal's publisher. "We know that low-density lipoprotein receptor binds to apoE, yet its potential role in Alzheimer's disease pathogenesis remains unclear."
In the new study, Holtzman and his colleagues genetically engineered mice that overexpressed low-density lipoprotein receptor, or LDLR, in the brain and bred them with mice engineered to feature key brain changes associated with Alzheimer's disease, including A-beta accumulation.
Overexpression of LDLR decreased brain apoE levels by 50 to 90 percent, resulting in significant reductions in plaque formation and neuroinflammatory responses, the researchers found.
"Our study clearly demonstrates the beneficial effects of LDLR overexpression in the brain on pathogenic A-beta aggregation and subsequent neuroinflammatory responses," Holtzman said. "Given the results from these studies, the therapeutic potential of previously identified compounds and potential new agents, which regulate LDLR in peripheral tissues, merits additional testing in animal models of A-beta amyloidosis."
The U.S. National Institute on Aging has more about Alzheimer's disease.