Brain Entry and Exit Consortium: How Does Vascular Fatty Acid Metabolism Regulate the Pathophysiology of Alzheimer’s Disease?

Alzheimer’s disease (AD) is a debilitating chronic neurodegenerative disease that is the leading cause of dementia and involves memory loss, disorientation, language issues, and many other behavioral abnormalities. Recently, it has been suggested that dysfunction of blood vessels in the brain may contribute to the onset and progression of this devastating disease. Despite the potential importance, very little is known about how the blood vessels of the brain actually change in patients with AD and how these changes affect disease pathology. Our goal is to identify the molecular changes in the blood vessels of patients with AD and then use cellular, molecular, and genetic approaches to determine how these changes affect blood vessel function and the progression of this devastating neurodegenerative disease. Interestingly, we found that there is a downregulation of lipid synthesis in the blood vessels of patients with AD, and we hypothesize that this loss of vascular lipids leads to changes in vascular function that drive neuroinflammation, which is then critical to the neurodegeneration observed in patients with AD. In this proposal, we aim to identify the role of brain vascular lipid metabolism in regulating brain vascular function and then determine how this affects the progression of AD. Our ultimate goal is to determine whether targeting brain vascular lipid metabolism may be therapeutic for the treatment of AD.