Roles of Tau Oligomers in Alzheimer's Vasculopathy

Tau 寡聚体在阿尔茨海默病血管病变中的作用

• 批准号: 10405024
• 负责人: JAMES C LEE
• 金额: $ 38.89万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10405024
• 关键词: 3xTg-AD mouse; Actins; Adhesions; Affect; Age; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease diagnosis; Alzheimer' s disease patient; Amyloid beta-Protein; Angiography; Atomic Force Microscopy; Automobile Driving; Biochemical; Biophotonics; Blood - brain barrier anatomy; Blood Vessels; Brain; Caliber; Cell Adhesion Molecules; Cell physiology; Cell surface; Cells; Characteristics; Clinical; Cytoplasm; Cytoskeleton; Cytosolic Phospholipase A2; Defect; Deposition; E-Selectin; Extracellular Fluid; Fluorescence Microscopy; Ganglionic Layer; Gender; Human; ICAM2 gene; Infiltration; Inflammation; Inflammatory; Intercellular adhesion molecule 1; Lead; Leukocytes; Measures; Mechanics; Mediating; Membrane; Methods; Mus; NADPH Oxidase; Nerve Degeneration; Neurofibrillary Tangles; Neurons; Optical Coherence Tomography; Oxidants; Oxidative Stress; P-Selectin; Pathology; Pathway interactions; Phosphorylation; Physiological; Probability; Reporting; Research; Resolution; Retina; Role; Selectins; Side; Study models; Testing; Tg2576; Therapeutic; Thick; Thinness; Transgenic Mice; Up-Regulation; Vascular Cell Adhesion Molecule-1; Vascular Diseases; amyloid pathology; brain endothelial cell; density; early detection biomarkers; extracellular; indexing; innovation; insight; interdisciplinary approach; mechanical force; migration; monocyte; mouse model; neurovascular; oAβ; p65; peripheral blood; polymerization; protein expression; response; retina blood vessel structure; statistics; tau Proteins; tau aggregation

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.

细胞外寡聚tau （o-tau）和o-tau的血管沉积在阿尔茨海默氏症的大脑中被观察到