Cerebrovascular Risk Factors for Alzheimer's Disease

Disturbances in the cerebrovascular system, including hypoperfusion, likely contribute to Alzheimer's disease (AD) pathogenesis and cerebral amyloid angiopathy (CAA), the latter often coexists with AD. APOE4 is a strong genetic risk factor for both AD and CAA. APOE plays critical roles in multiple biological processes necessary for maintaining central nervous system homeostasis yet the cerebrovascular effects of apoE are poorly understood. Studies in Dr. Bu's lab focus on the effects of APOE isoforms on maintaining cerebrovascular homeostasis and the metabolism of amyloid beta (abeta). The lab employs cell culture techniques (including primary cell cultures and human induced pluripotent stem cell (iPSC)-derived cells, unique in vivo mouse models, in vitro blood-brain barrier (BBB) and 3-D vessel models, and postmortem human brain tissues. The overall goal of these studies is to define the cerebrovascular effects of APOE isoforms and to explore the potentials of APOE-targeted therapies for AD.