High-Density Lipoprotein in Alzheimer's Disease
Over the funding period we aim to mechanistically characterize how high-density lipoprotein, a blood lipid transporter modulates cerebrovascular health in the context of Alzheimer's disease. We previously showed that HDL promotes brain vessel health in Alzheimer’s disease. In particular we found that HDL containing apolipoprotein E (apoE) are the most active. However HDL is circulating in the blood and to promote vessel health it must interact with the vessel wall, a process that remains poorly understood. Here we will measure how HDL interacts with the different cells composing the brain vessels. In addition, because apoE is the major genetic risk factor for Alzheimer’s disease, we will analyze how apoE genotypes influence HDL interaction with brain vessel cells.
Our proposal builds upon human based bioengineered brain vessels cultured in the test tube that retain both functional and anatomical properties of native vessels. Because each component of these vessels are modifiable and human blood-lipid carried can be circulating through these vessels, they offer a unique approach to mechanistically study biological and pathological questions in a human relevant system. Our proposal will help to better understand the role of blood circulating lipid carriers in Alzheimer’s disease ultimately helping to the development of lipoprotein based or targeted therapeutics.