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Using Human Bioengineered Cerebral Vessels to Explore How Native APOE Affects Cerebrovascular Properties Relevant to Alzheimer’s Disease

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The brain contains approximately 400 miles of specialized blood vessels that protect and nourish it. One important function of these cerebral vessels is to allow amyloid beta, a peptide central to Alzheimer’s disease, to exit the brain. As people age, this function often becomes impaired, and amyloid beta then becomes stuck in the vessels and contributes to other changes that lead to full-blown AD. Risk factors for AD, including genetic (APOE) and lifestyle (exercise, cholesterol) issues, can affect function of cerebral vessels in ways we don’t yet understand. My lab therefore has invented a way to grow human cerebral blood vessels with proper anatomy and function in a test tube. These three-dimensional vessels contain human endothelial cells that form the blood-brain barrier, smooth muscle cells that control blood flow and astrocytes that produce APOE. In this project we will study how APOE affects amyloid beta clearance through and inflammation of cerebral vessels.