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Tau in the Eye and Brain

眼睛和大脑中的 Tau 蛋白

基本信息

批准号：
9289398
负责人：
Rakez Kayed
金额：
$ 265.16万
依托单位：
UNIVERSITY OF TEXAS MED BR GALVESTON
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9289398
关键词：
Abbreviations Advanced Development Affect Alzheimer disease prevention Alzheimer&apos s Disease Antibodies Atomic Force Microscopy Behavioral Biological Markers Brain Brain Pathology Brain region Cognitive Complex Data Development Diagnosis Disease Disease Progression Drug Targeting Early Intervention Electroretinography Encephalitis Eye Functional disorder Human Immunohistochemistry Impaired cognition Inflammation Injectable Investigation Laboratories Lewy Body Dementia MAPT gene Memory impairment Methods Molecular Conformation Monitor Monoclonal Antibodies Mus Nerve Degeneration Neurofibrillary Tangles Neuronal Dysfunction Neurons Optical Coherence Tomography Outcome Study Pathologic Pathology Pathway interactions Patients Performance Phenotype Prevention Progressive Supranuclear Palsy Research Proposals Retina Retinal Retinal Degeneration Retinal Ganglion Cells Rod Outer Segments Role Sampling Synaptic Transmission Tauopathies Testing Therapeutic Therapeutic Effect Transgenic Mice Traumatic Brain Injury Visual base design disease phenotype ganglion cell hTau Mice in vivo innovation insight intravitreal injection mouse model neurotoxicity non-invasive imaging noninvasive diagnosis novel novel strategies novel therapeutic intervention object recognition paired helical filament pre-clinical protein aggregate research clinical testing response tau Proteins tau aggregation tool

项目摘要

PROJECT SUMMARY/ABSTRACT Progressive accumulation of microtubule-associated protein (tau) is a defining feature of Alzheimer's disease (AD) and a number of other disorders termed tauopathies. Recent studies from our laboratories, confirmed by others, demonstrated that tau oligomers constitute distinctly toxic and pathologically significant tau species able to spread in tauopathy brain, likely through inter-synaptic transmission. However, precise investigation of tau oligomer spreading is hindered by the complexity of the neuronal network. Methods to effectively diagnose AD and other tauopathies at early stages and monitor their progress are also lacking. In addition to cognitive abnormalities, AD patients show visual anomalies. In this application, we will test the hypothesis that tau pathology in the retina may predict tau-related dysfunction in the brain, making it an excellent platform to study the propagation of tau oligomeric strains, detect and monitor the progression of AD and other tau-related disorders, and evaluate the efficacy of our newly developed tau oligomer-specific monoclonal antibodies (TOMAs) at targeting different tau oligomeric strains. Outcomes from this study will provide clear pathways of oligomer spreading and aid in the development of novel approaches to monitor and treat tauopathies.

项目总结/摘要微管相关蛋白（tau）的进行性积累是阿尔茨海默病的一个定义性特征 (AD)以及许多其他称为Tau蛋白病的疾病。我们实验室的最新研究证实，其他研究表明，tau寡聚体构成明显有毒和病理学显著的tau种类，能够在tau蛋白病的大脑中传播，可能通过突触间传递。然而，精确调查 tau寡聚体扩散受到神经元网络复杂性的阻碍。有效诊断的方法 AD和其他tau蛋白病的早期阶段，并监测其进展也缺乏。除了认知 AD患者表现出视觉异常。在本申请中，我们将测试tau 视网膜病理学可以预测大脑中与tau相关的功能障碍，使其成为一个绝佳的研究平台 tau寡聚体菌株的繁殖，检测和监测AD和其他tau相关疾病的进展疾病，并评估我们新开发的tau寡聚体特异性单克隆抗体的疗效在靶向不同的tau寡聚体菌株方面，这项研究的结果将提供明确的途径，本发明的目的在于抑制低聚物扩散，并有助于开发监测和治疗tau蛋白病的新方法。