LRP1 In Amyloid Beta Metabolism And CAA
MentorGuojun Bu, PhD Washington University
Mounting pathological studies from Alzheimer's disease patients have shown that amyloid-beta deposits are found not only in senile plaques but also in cerebral blood vessel as cerebral amyloid angiopathy (CAA), a major cause of intracranial hemorrhage and progressive dementia in elderly population. Amyloid beta deposition in CAA is detected primarily in the smooth muscle layer of cerebral arteries. The low-density lipoprotein receptor-related protein 1 (LRP1), known as amyloid-beta scavenger receptor, is abundantly expressed in smooth muscle cells. Therefore, the specific aims are designed to provide a comprehensive assessment of the function of LRP1 in amyloid beta metabolism and in CAA pathogenesis as well as the effect of amyloid beta on LRP1 expression and function in smooth muscle cells.
The deposition of amyloid beta in brain blood vessels causes brain bleeding and progressive dementia in aged individuals. Because amyloid beta scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1), is abundantly expressed in brain vessels, we are focusing on the association of LRP1 with the amyloid beta deposition on brain vessel walls. The specific aims of this project are designed as follows; 1) Characterization of LRP1-mediated metabolism of amyloid beta in blood vessels, 2) Analyze the effects of the amyloid-beta on LRP1 expression and function, and 3) Define the role of LRP1 in amyloid deposition on brain blood vessels using animal models.