Harvard Catalyst Profiles

Alzheimer's Association

Identifying Astrocyte-Mediated Vasomotion Underlying AD Pathogenesis

Role Description: The goal of this study is to elucidate the mechanisms underlying glymphatic dysfunction in Alzheimer's disease, focusing specifically on the role of astrocytes in mediating changes in arteriole vasomotion and their impact on the brain's waste clearance system. Alzheimer's disease is characterized by the accumulation of beta-amyloid and tau proteins in the brain, forming plaques and tangles that contribute to cognitive decline. While the exact causes of these protein accumulations remain unclear, impairments in the glymphatic system, which is responsible for removing waste products from the brain, are suspected to play a critical role. In healthy individuals, the glymphatic system, facilitated by brain blood vessels including arterioles, efficiently clears waste, with arterioles' vasomotion—periodic dilation and contraction—believed to assist in guiding waste out of the brain. Astrocytes, a type of support cell in the brain, are known to regulate this vasomotion and thus are crucial in maintaining effective waste clearance. However, in Alzheimer’s, the function of this system may be compromised, leading to the build-up of neurotoxic proteins. This study aims to investigate how astrocytic regulation of arteriole vasomotion changes in Alzheimer's and how these changes contribute to glymphatic dysfunction. By understanding these mechanisms, we hope to uncover potential therapeutic targets to enhance glymphatic function, thereby mitigating one of the pathological features of Alzheimer's disease and possibly slowing its progression.

Role: PI