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2012 Grants - Bu
LRP1 and HSPG in Cerebrovascular Clearance of Abeta
Guojun Bu, Ph.D.
Mayo Clinic Jacksonville
2012 Investigator-Initiated Research Grant
Beta-amyloid (also known as Abeta) is a protein fragment that accumulates into amyloid plaques in the brain, one of the hallmark features of Alzheimer's disease. Beta-amyloid is also found in healthy brains, and there is growing evidence that defects in the clearance of beta-amyloid from the brain may account for some forms of Alzheimer's disease. There are several biochemical pathways for clearance of beta-amyloid. One of these pathways involves binding of the protein fragment to the cell surface, followed by transport into the cell and degradation by cellular machinery.
Guojun Bu, Ph.D., and colleagues have been studying the process by which beta-amyloid binds to the cell surface before degradation. They have identified two proteins on the cell surface, LRP1 and HSPG, that bind to beta-amyloid and direct it to the cellular machinery responsible for degradation. These proteins are especially important in brain blood vessels, where excessive beta-amyloid leads to disruption of blood flow, contributing to brain damage. Dr. Bu and colleagues have proposed using genetic engineering techniques to study how changes in the levels of LRP1 and HSPG affect the clearance of beta-amyloid in animal models. These studies will improve our understanding of how beta-amyloid is cleared from the brain, and may identify targets for drugs to combat the development of amyloid plaques.