VA Biorepository Brain Bank

VA 生物储存库脑库

• 批准号: 10265402
• 负责人: Christopher B Brady
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10265402
• 关键词: Address; Adult; Affect; Age; Age Factors; Amyotrophic Lateral Sclerosis; Anatomy; Arizona; Autopsy; Behavior assessment; Behavioral; Biological Availability; Biological Markers; Boston; Brain; Caring; Cessation of life; Clinical; Clinical Data; Clinical Management; Cognitive; Collaborations; Collection; Communities; Consensus; Country; Craniocerebral Trauma; Cryopreservation; DNA Sequence Alteration; Data; Development; Diagnosis; Disease; Disease Progression; Enrollment; Environmental Exposure; Environmental Risk Factor; Etiology; Exposure to; Family member; Financial cost; Freezing; Functional disorder; Funding; Future; Generations; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Risk; Genetic study; Genomics; Health; Healthcare Systems; High Prevalence; Human; Impaired cognition; Incidence; International; Investments; Link; Low Prevalence; Measurement; Medical Informatics; Microglia; Modeling; Muscular Dystrophies; National Institute on Aging; Nature; Neuraxis; Neurodegenerative Disorders; Organism; Paralysed; Pathologic; Pathology; Patients; Persons; Pharmacotherapy; Pilot Projects; Positioning Attribute; Prevalence; Prospective cohort study; Proteomics; Research; Research Personnel; Research Project Grants; Research Support; Resources; Risk; Sampling; Services; Site; Spinal Cord; Spouses; Telephone; Time; Tissue Banks; Tissue Sample; Tissues; United States Department of Veterans Affairs; Veterans; Veterans Health Administration; amyotrophic lateral sclerosis therapy; biobank; care costs; case control; chronic traumatic encephalopathy; clinical care; cohort; cost; data management; disability; effective therapy; follow-up; genome sequencing; improved; military service; military veteran; mouse model; nervous system disorder; neuropathology; novel marker; operation; outreach program; phenylmethylpyrazolone; programs; tissue processing; urinary; whole genome

Amyotrophic lateral sclerosis (ALS) is an adult onset, rapidly fatal, neurodegenerative disease of unknown etiology. Studies have indicated a higher prevalence of ALS among veterans than among civilians, and in 2008, ALS was declared a fully compensable condition by the Department of Veterans Affairs (VA). The VA funds research projects such as the VA Biorepository Brain Bank (VABBB) to support ALS research and improve clinical care. Establishing large national cohorts essential for ALS research is limited by the low prevalence (6-8 cases per 100,000) and short survival time (3-5 years) of persons with ALS (PALS). This is particularly true for efforts to develop biorepositories that collect central nervous system (CNS) tissue samples annotated with clinical information essential to biomedical ALS research. Although a number of mouse models have been developed to study ALS, these models are limited and the need for research quality human CNS tissue for genomic and proteomic research in ALS is critical. The VABBB is presently the only national prospective cohort study and CNS tissue bank in the U.S. that is enrolling and conducting ongoing follow-up on veterans with ALS. The VABBB is a multi-site collaboration among VA Boston Healthcare System (VABHS) and the Southern Arizona VA Healthcare System (SAVAHCS). The VABBB utilizes the strengths across the Boston and Tucson sites in enrollment, assessment, tissue banking operations, neuropathological diagnosis, medical informatics and data management. The VABBB cohort is notable for its size (over 300 PALS), the amount and quality of CNS tissue and clinical data available, and especially for the relatively long duration and slow disease progression in this unique cohort. Tissue and clinical data from the VABBB are available for international distribution to qualified researchers. In this application, we seek to further our support of cutting edge ALS research and enhance the value of VA’s investment in the VABBB. Over the next four years our specific aims are: 1) To continue and further enhance the VABBB as the nation’s only national prospective cohort study and central nervous system (CNS) tissue/biofluid bank supporting international ALS research; 2) Leverage the resources and staffing of the VABBB to conduct new state-of-the-art genetic, biomarker, environmental exposure and neuropathological analyses on banked biofluid and tissue samples; and 3) To provide a state-of-the-art characterization of cognitive and behavioral dysfunction in our cohort to support research on the pathophysiology and clinical management of ALS. Specific Aim 1 will involve 1) generation of a larger and more diverse CNS tissue collection from Veteran PALS along with spousal and Veteran controls; 2) enhanced antemortem assessment of enrollees and postmortem biofluid and tissue collection and analyses; and 3) development of an international outreach program to promote the use of our tissue and data by ALS researchers. In Specific Aim 2, we will 1) conduct whole genome sequencing on our tissue; 2) cryopreserve live microglia from post-mortem tissue for cellular studies; 3) analyze samples for current and newly discovered ALS biomarkers (e.g., urinary p75ECD) and environmental exposures to enhance the value of our tissue in validating biomarkers and environmental exposures against ALS neuropathology; 4) assess our CSF quality to promote a diversity of ALS research, and 5) conduct neuropathological analyses with rigorous quantitative and semi-quantitative measurements of the histopathological, immunohistochemical, and anatomical findings to examine emerging links between head trauma, ALS, and overlapping pathologies such as CTE. Regarding Specific Aim 3, we will enhance our longitudinal cognitive/behavioral telephone/mail assessment of our cohort to facilitate clinicopathological and genetic studies of ALS. The availability of high quality fixed and frozen CNS tissue and data from the VABBB will facilitate research into genetic and environmental risk factors and clinical pathological relationships in ALS.

肌萎缩侧索硬化症 (ALS) 是一种成人发病、迅速致命的神经退行性疾病，病因不明 研究表明，退伍军人中 ALS 的患病率高于平民，并且 2008 年，退伍军人事务部 (VA) 宣布 ALS 为可全额赔偿的疾病。 资助 VA Biorepository Brain Bank (VABBB) 等研究项目，以支持 ALS 研究和 建立对 ALS 研究至关重要的大型国家队列受到低水平的限制。 ALS (PALS) 患者的患病率（每 100,000 人中有 6-8 例）且生存时间短（3-5 年）。 对于开发收集中枢神经系统 (CNS) 组织样本的生物样本库的努力尤其如此 注释了生物医学 ALS 研究所必需的临床信息，尽管有许多小鼠模型。 已经开发用于研究 ALS，这些模型是有限的，并且需要研究高质量的人类中枢神经系统 VABBB 是目前唯一的国家级组织，用于 ALS 基因组和蛋白质组学研究至关重要。 美国的前瞻性队列研究和中枢神经系统组织库正在招募并持续进行随访 VABBB 是 VA 波士顿医疗系统 (VABHS) 之间的多站点合作项目。 以及南亚利桑那州 VA 医疗系统 (SAVAHCS)，VABBB 充分利用了整个州的优势。 波士顿和图森站点负责登记、评估、组织库操作、神经病理学诊断、 VABBB 队列以其规模（超过 300 个 PALS）而闻名。 可用的中枢神经系统组织和临床数据的数量和质量，特别是对于相对较长的持续时间和 来自 VABBB 的组织和临床数据可用于减缓这一独特队列的疾病进展。 在此应用程序中，我们寻求进一步的切割支持。 加强 ALS 研究并提高 VA 在未来四年内对 VABBB 的投资价值。 具体目标是： 1) 继续并进一步加强 VABBB 作为国家唯一的国家级前景 支持国际 ALS 研究的队列研究和中枢神经系统 (CNS) 组织/生物体液库； 利用 VABBB 的资源和人员进行新的最先进的遗传、生物标志物、 对储存的生物液体和组织样本进行环境暴露和神经病理学分析；以及 3) 提供我们队列中认知和行为功能障碍的最先进的表征，以支持 ALS 病理生理学和临床治疗的研究具体目标 1 将涉及 1) 的产生。 来自退伍军人 PALS 以及配偶和退伍军人对照的更大、更多样化的 CNS 组织集合； 2) 加强对参与者的死前评估以及死后生物体液和组织的收集和分析； 3) 制定国际推广计划，以促进 ALS 使用我们的组织和数据 在具体目标 2 中，我们将 1) 对我们的组织进行全基因组测序；2) 冷冻保存； 来自死后组织的活小胶质细胞用于细胞研究；3) 分析当前和新发现的样本 ALS 生物标志物（例如尿液 p75ECD）和环境暴露可提高我们组织的价值 根据 ALS 神经病理学验证生物标志物和环境暴露 4) 评估我们的 CSF 质量； 促进 ALS 研究的多样性，5) 进行严格的定量和神经病理学分析 组织病理学、免疫组织化学和解剖学结果的半定量测量 研究头部外伤、ALS 和 CTE 等重叠病理之间的新联系。 具体目标 3，我们将加强对我们队列的纵向认知/行为电话/邮件评估 促进 ALS 的临床病理学和遗传学研究。 来自 VABBB 的组织和数据将促进对遗传和环境风险因素以及临床的研究 ALS 中的病理关系。