Interdisciplinary Research Network on Biologically Active Tau Aggregate Polymorphs from Alzheimer's Disease and Related Dementias

阿尔茨海默病和相关痴呆症生物活性 Tau 聚集多晶型跨学科研究网络

• 批准号: 10436894
• 负责人: DAVID EISENBERG
• 金额: $ 154.49万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10436894
• 关键词: Address; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Amyloid beta-Protein; Antibodies; Appearance; Area; Atomic Force Microscopy; Biochemical; Biological; Biological Models; Centrifugation; Characteristics; Chemicals; Clinical; Communities; Cryoelectron Microscopy; Detection; Diagnosis; Disease; Disease Vectors; Electrons; Filament; Fluorescence Microscopy; Genetic Polymorphism; Goals; High Prevalence; Higher Order Chromatin Structure; Human; Immunologics; Interdisciplinary Study; Lesion; Mass Spectrum Analysis; Measurement; Methods; Mission; Molecular; Morphology; Nerve Degeneration; Neurodegenerative Disorders; Pathogenesis; Pathology; Peptide Hydrolases; Pick Disease of the Brain; Polymorph; Post-Translational Protein Processing; Preparation; Progressive Supranuclear Palsy; Proteins; Proteomics; Protocols documentation; Radio; Reagent; Recombinants; Reproducibility; Research; Research Support; Resources; Role; Sampling; Seeds; Severity of illness; Source; Specimen; Staging; Standardization; Structure; Surrogate Markers; Tauopathies; Tissues; Toxic effect; Validation; alpha synuclein; animal tissue; biophysical analysis; brain tissue; comorbidity; corticobasal degeneration; diagnostic signature; disease diagnosis; human disease; human tissue; innovation; novel diagnostics; novel therapeutic intervention; protein TDP-43; protein aggregation; synaptic function; tau Proteins; tau aggregation; tool; transmission process

PROJECT SUMMARY Tau aggregation is a shared pathology of Alzheimer's disease and related dementias known as tauopathies. Because each disorder develops a unique combination of aggregate polymorphisms and co-morbidities that may influence the course and severity of disease, elucidating the relationship between tau aggregate structure and biological activity has become a high priority in the field. Advances to date have been limited, however, by the lack of rigorously standardized aggregate preparations from each form of tauopathy and by the absence of tools needed to selectively detect their presence in biological models and clinical specimens. The proposed Interdisciplinary Research Network on Biologically Active Tau Aggregate Polymorphs seeks to address this need by (1) isolating a full range of biologically active tau aggregates from authentic Alzheimer's disease, Corticobasal Degeneration, Progressive Supranuclear Palsy, and Pick's disease brain tissue, (2) establishing their structures through biophysical analysis, (3) developing probe sets for their selective detection, and (4) disseminating reliably vetted samples and lab-ready protocols for their handling and storage to the broader research community. In accomplishing these goals, the network will support research into the molecular basis of tauopathy pathogenesis and catalyze efforts toward creating novel diagnostic and therapeutic strategies specifically tailored against toxic tau aggregate polymorphs.

项目概要 Tau 聚集是阿尔茨海默病和相关痴呆（称为 tau 病）的共同病理学。 因为每种疾病都会形成一种独特的聚合多态性和合并症组合，可能会导致 影响疾病的病程和严重程度，阐明 tau 聚集结构与疾病之间的关系 生物活性已成为该领域的高度优先事项。然而，迄今为止的进展受到限制 每种形式的 tau 蛋白病缺乏严格标准化的聚合制剂，并且缺乏工具 需要选择性地检测它们在生物模型和临床标本中的存在。拟议的 生物活性 Tau 聚集多晶型跨学科研究网络致力于满足这一需求 通过 (1) 从真正的阿尔茨海默氏病 Corticobasal 中分离出全系列具有生物活性的 tau 聚集体 变性、进行性核上性麻痹和皮克氏病脑组织，(2) 建立其结构 通过生物物理分析，(3) 开发用于选择性检测的探针组，以及 (4) 传播 经过可靠审查的样品和实验室就绪协议，用于处理和存储更广泛的研究 社区。为了实现这些目标，该网络将支持 tau 蛋白病的分子基础研究 发病机制并促进创造专门定制的新型诊断和治疗策略的努力 对抗有毒的 tau 聚集体多晶型物。