Vascular Regenerative Therapy for Alzheimer’s Disease

Alzheimer’s disease (AD) is a major cause of dementia in elderly. The amyloid-β (Aβ) peptides deposit in the brain parenchyma as senile plaques and in the cerebrovasculature as cerebral amyloid angiopathy (CAA), both are hallmarks of AD pathology. Epidemiologically, cerebrovascular damages caused by diabetes mellitus or stroke increase the risk for AD. Cerebral hypoperfusion precedes cognitive decline and neurodegeneration in AD. Our recent work has also demonstrated that cerebrovasculature plays critical roles in Aβ clearance. Therefore, we aim to develop novel regenerative therapy for AD by restoring cerebral vasculature function and neural integrity through transplantation of induced pluripotent stem cell (iPSC)-derived specialty cells. Specifically, we will co-inject iPSC-derived vascular progenitor cells (VPCs) and neural stem cells (NSCs) into mouse brain to promote synergistic effects for regeneration of both cerebral vessels and neurons as neurovascular interactions play critical roles in neurogenesis and angiogenesis. Therefore, the overall goal of this proposed study is to investigate the effects of regenerative therapy through transplantation of iPSC-derived VPCs and neurospheres on Aβ clearance, amyloid pathology and cognitive function in amyloid model mice. Our innovative approach could lead to development of novel therapeutic methods to treat AD.