Roles of Tau Oligomers in Alzheimer's Vasculopathy

细胞外寡聚tau蛋白（o-tau）和o-tau蛋白的血管沉积已在阿尔茨海默氏症患者的脑中观察到。 AD患者。在这个项目中，我们建议研究如何直接相互作用的o-tau与 人脑微血管内皮细胞（HBMEC）的基底外侧影响其功能，包括 氧化应激、炎症、粘附分子表达、膜系链粘附和跨内皮细胞粘附。 单核细胞通过NADPH氧化酶、胞浆磷脂酶A2 和NFκB。由于视网膜是大脑的一部分，我们也采用了非侵入性的光学相干断层扫描 (OCT)和OCT血管造影术（OCTA）（即OCT/OCTA），以研究微血管特征， 神经变性，如通过神经节层厚度（GLT）量化的，以及它们与寡聚 研究人tau蛋白对Tg AD小鼠模型视网膜中oAβ、o-tau蛋白含量的影响 和淀粉样蛋白病理学，包括APPswe/PSEN 1dE 9和3xTg AD小鼠。该项目将填补研究空白 通过提供关于粘附的信息， HBMEC中对o-tau的机械反应，以及HBMEC中视网膜血管网络特征和GLT的变化。 与Aβ和o-tau的关系，并最终通过以下方式提供对AD治疗的治疗策略的见解： 调节tau的作用。

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.