Roles of Tau Oligomers in Alzheimer's Vasculopathy

在阿尔茨海默病患者的脑组织中观察到了细胞外寡聚体tau(o-tau)和o-tau的血管沉积 疾病(AD)患者。在这个项目中，我们建议研究o-tau与 人脑微血管内皮细胞(HBMECs)的基底外侧影响其功能，包括 氧化应激、炎症、黏附分子表达、膜系绳黏附和跨内皮细胞 NADPH氧化酶、胞浆磷脂酶A2激活对单核细胞迁移的影响 由于视网膜是大脑的一部分，我们也使用了非侵入性的光学相干断层扫描技术(Non-侵入性光学相干断层扫描 (OCT)和OCT血管成像(OCTA)(即OCT/OCTA)以研究微血管特征和 神经节层厚度(GLT)量化的神经退行性变及其与寡聚体的关系 TGAD小鼠模型视网膜淀粉样蛋白β(OAβ)和o-tau含量的变化及人tau对其影响的研究 淀粉样变性包括APPswe/PSEN1dE9和3xTg AD小鼠。这个项目将填补这一研究空白 细胞外o-tau与阿尔茨海默病神经血管异常之间的关系 人视网膜微血管内皮细胞对o-tau的机械反应以及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为AD的治疗策略提供见解 调节牛磺酸的作用。

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.