Cerebrovasculature in AD and Dementia
Disturbances in the cerebrovascular system, including hypoperfusion and loss of blood-brain barrier (BBB) integrity, likely contribute to Alzheimer's disease (AD) pathogenesis and cerebral amyloid angiopathy (CAA), which often coexists with AD. Importantly, APOE4 is a strong genetic risk factor for both AD and CAA. While it is increasingly recognized that apoE plays a critical role in multiple biological processes necessary for maintaining central nervous system homeostasis, the cerebrovascular effects of apoE are not fully understood.
Dr. Bu's lab is focused on defining the cerebrovascular effects of apoE isoforms to explore the potentials of apoE- and vascular-targeted therapies for AD and aging-related cognitive decline.
Studies in the Neurobiology of Alzheimer's Disease Lab aim to determine the effects of apoE isoforms on maintaining cerebrovascular homeostasis and the metabolism of amyloid-beta. Toward this, the lab takes advantage of multiple disease-modeling systems. These include human iPSC-derived vascular cells, in vitro BBB and 3D vessel models, unique animal models, and postmortem human brain tissues.
Yamazaki Y, Liu CC, Yamazaki A, Shue F, Martens YA, Chen Y, Qiao W, Kurti A, Oue H, Ren Y, Li Y, Aikawa T, Cherukuri Y, Fryer JD, Asmann YW, Kim BYS, Kanekyio T, Bu G. Vascular ApoE4 impairs behavior by modulating gliovascular function. Neuron. 2021; doi:10.1016/j.neuron.2020.11.019
Liu CC, Yamazaki Y, Heckman MG, Martens YA, Jia L, Yamazaki A, Diehl NN, Zhao J, Zhao N, DeTure M, Davis MD, Felton LM, Qiao W, Li Y, Li H, Fu Y, Wang N, Wren M, Aikawa T, Holm ML, Oue H, Linares C, Allen M, Carrasquillo MM, Murray ME, Peterson RC, Ertekin-Taner N, Dickson DW, Kanekiyo T, Bu G. Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease. Alzheimer's & Dementia. 2020; doi:10.1002/alz.12104
Yamazaki Y, Shinohara M, Yamazaki A, Ren Y, Asmann YW, Kanekiyo T, Bu G. ApoE (Apolipoprotein E) in brain pericytes regulates endothelial function in an isoform-dependent manner by modulating basement membrane components. Arteriosclerosis, Thrombosis, and Vascular Biology. 2020; doi:10.1161/ATVBAHA.119.313169