Roles of Tau Oligomers in Alzheimer's Vasculopathy

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Extracellular oligomeric tau (o-tau) and vascular deposition of o-tau has been observed in brains of Alzheimer's disease (AD) patients. In this project, we propose to examine how the direct interactions of o-tau with the basolateral side of human brain microvascular endothelial cells (HBMECs) impact their function, including oxidative stress, inflammation, adhesion molecule expression, membrane tether adhesion, and transendothelial migration of monocytes through activations of NADPH oxidase, cytosolic phospholipase A2 and NFκB. As retina is a part of the brain, we also employ the non-invasive optical coherence tomography (OCT) and OCT angiography (OCTA) (i.e. OCT/OCTA) to study microvascular characteristics and neurodegeneration, as quantified by the ganglion layer thickness (GLT), and their relations to oligomeric amyloid-β (oAβ), and o-tau contents in retinas of Tg AD mouse models for studying the influences of human tau and amyloid pathology including APPswe/PSEN1dE9 and 3xTg AD mice. This project will fill the research gap between extracellular o-tau and neurovascular abnormalities in AD by providing information regarding adhesion mechanical responses to o-tau in HBMECs, and changes in retinal vessel network characteristics and GLT in relations to Aβ and o-tau, and ultimately provide insights into therapeutic strategies for AD treatment by regulating tau's effects.