Massachusetts General Hospital (MGH) investigators have determined one of the recently identified genes contributing to the risk of late-onset Alzheimer's disease regulates the clearance of the toxic amyloid beta (A-beta) protein that accumulates in the brains of patients with the disease. In their report receiving advance online publication in Neuron, the researchers describe a protective variant of the CD33 gene that promotes clearance of A-beta from the brain. They also show that reducing expression of CD33 in immune cells called microglia enhances their ability to clear away A-beta protein, raising the possibility that blocking CD33 activity could help the brain's immune system remove A-beta.
"Our findings show, for the first time, a "switch" that controls how fast microglial cells can clear A-beta protein from the brain as we age -CD33 is the key," says Rudolph Tanzi, director of the Genetics and Aging Research Unit in the MGH Department of Neurology and senior author of the Neuron paper. "If we can find a way of safely inactivating CD33 on microglia, we should be able to slow the accumulation of A-beta in aging brains and hopefully reduce risk for Alzheimer's disease."
In 2008, as part of the Alzheimer's Genome Project, Tanzi's team identifed four novel genes containing variants that increased the risk of late-onset Alzheimer's, the most common form of the devastating neurological disorder.