Endothelial progenitor cells and neurovascular injury in the aging

Project Summary The proposed study will investigate endothelial progenitor cells (EPCs) taken from blood samples from older adults at risk for dementia due to aging, genetics, Alzheimer’s disease pathophysiological changes and/or cerebral small vessel disease. Extensive studies have focused on brain and cognitive markers of resilience to Alzheimer’s disease, but far fewer studies have focused on the role of potentially protective vascular factors such as EPCs. Proposed studies will utilize blood markers of EPCs and will culture EPCs from older adult blood samples to investigate whether EPCs may predict whether someone remains cognitively normal despite the presence of Alzheimer’s and vascular brain changes or whether they begin to decline cognitively. Studies will also investigate whether EPC levels predict cerebrovascular changes, including deficits in the integrity of the blood-brain barrier. Finally, EPCs cultured from older adults with and without Alzheimer’s or vascular brain pathological changes will be studied and compared in their ability to grow, function and form a blood-brain barrier in a chip-based vascular microbrain model that mimics the cerebral microvasculature in vitro. Findings from in vitro EPC studies will then be compared with findings from brain imaging measures of cerebrovascular function and blood-brain barrier integrity.