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2006 Grant - Lee
Effects of Beta-Amyloid Peptide on Adhesion Mechanics of Cerebral Endothelium
James Lee, Ph.D.
University of Missouri
2006 New Investigator Research Grant
Although blood vessels permeate the central nervous system, they never empty their contents into it. Instead, molecules must pass through the blood vessel walls in order to enter or leave the brain. For small sugars, ions and other nutrients, this is not a problem. But for larger molecules the physical barrier presented by the blood vessel walls, what scientists call the blood-brain barrier, is insurmountable. The blood-brain barrier thus protects the brain from intruders.
But sometimes the barrier can be breached. In Alzheimer's disease, for example, immune cells not normally found in the central nervous system are detected in the brain at autopsy. Some scientists believe that beta-amyloid, a sticky, toxic protein fragment that accumulates during progression of the disease, may weaken the blood-brain barrier and allow these cells to pass through it.
James Lee, Ph.D., and colleagues plan to examine what role beta-amyloid plays in the movement of these immune cells, or monocytes, into the brain. Specifically, they plan to examine the relationship between endothelial cells, specialized cells that line the blood vessel walls, and beta-amyloid.
For monocytes to pass through the blood vessel walls, they must first adhere to the lining of the blood vessel, whereupon they "crawl" along until they find a gap between two endothelial cells. For the initial binding to occur, the endo-thelial cells must have specific receptors, or docking proteins, called selectins on their cell surface. Lee and colleagues plan to examine what effect, if any, beta-amyloid has on the presence of selectins on the endothelial cells. They will also determine if statins, cholesterol-lowering drugs associated with a lower risk for Alzheimer's disease, may attenuate any effect of beta-amyloid on endothelial cells.