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. Pericytes are mural cells that line the outside of blood vessels and regulate various aspects of neurovascular function, such as vascular tone, blood-brain barrier function, and neuroinflammatory responses—all processes critical for brain health. Interestingly, dysfunction and even death of pericytes have been observed in patients with AD, suggesting that pericytes may play critical roles in the neurovascular dysfunction observed in patients with AD. Despite their potential importance, very little is known about how pericytes respond to insults in the AD brain, such as amyloid buildup and low oxygen levels. In this proposal, we will aim to understand the cellular and molecular mechanisms that drive the response of pericytes to disease, and then determine if we can modulate pericyte survival to limit the pathogenesis of AD. Our ultimate goal is to determine whether we can target brain pericytes to treat AD.
