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2006 Grant - Andreasson
Function of PGE2 Receptors in the Development of Alzheimer's Disease
Katrin Andreasson, M.D.
2006 Investigator-Initiated Research Grant
The causes of Alzheimer's disease are not well understood. Studies have shown that inflammation in the brain contributes to processes that damage neurons. The role of inflammation has prompted investigations to test the effect of currently available anti-inflammatory medications and to characterize more carefully what inflammatory mechanisms are at work in Alzheimer's.
The body produces several different prostaglandins, which have different functions and actions within the body. They also bind to different receptors-"docking sites" on the surface of cells-which mediate the effects of each prostaglandin. Katrin Andreasson, M.D., and colleagues have found that the receptor for one prostaglandin, prostaglandin E2 (PGE2), mediates inflamma-tion and the accumulation of beta-amyloid, a key feature of Alzheimer patho-logy, in genetically altered mice that develop an Alzheimer-like disorder.
Dr. Andreasson and colleagues will extend their research by studying how the PGE2 receptor mediates inflammation and enhances amyloid accumulation. They will study three different forms of the PGE2 receptor using molecular techniques. For these studies, they will utilize mice that exhibit many features of Alzheimer pathology and mice in which the gene for the PGE2 receptor has been deleted or down-regulated. These studies may provide insight into how inflammatory mediators in the body contribute to one of the key features of Alzheimer pathology and may suggest new therapeutic strategies.