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: 10657390
• 负责人: DAVID EISENBERG
• 金额: $ 155.45万
• 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/10657390
• 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 Progression; 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; Protomer; Reagent; Recombinants; Reproducibility; Research; Research Support; Resources; Role; Sampling; 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.

项目总结 Tau聚集是阿尔茨海默病和被称为tauopathy的相关痴呆的共同病理。 因为每种疾病都会发展出一种独特的聚合多态和共病的组合，这种组合可能 影响疾病的病程和严重程度，阐明tau集合体结构与疾病的关系 生物活动已成为该领域的高度优先事项。然而，到目前为止，进展受到了 缺乏每种形式的直肠疗法的严格标准化的集合制剂，以及缺乏工具 需要选择性地检测它们在生物模型和临床标本中的存在。建议数 生物活性Tau聚合体的跨学科研究网络试图满足这一需求 通过(1)从正宗的阿尔茨海默病皮质基底部分离出一系列具有生物活性的tau聚集体 变性、进行性核上性麻痹和Pick病脑组织，(2)建立其结构 通过生物物理分析，(3)研制选择性检测探针组，(4)推广 可靠地审查样品和实验室就绪协议，以便处理和存储到更广泛的研究中 社区。在实现这些目标的过程中，该网络将支持对直立面疗法分子基础的研究。 致病机制和催化努力，以创造新的诊断和治疗策略专门定制 对抗有毒的tau聚集态。