VA Biorepository Brain Bank

VA 生物储存库脑库

• 批准号: 8661513
• 负责人: Neil W. Kowall
• 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 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661513
• 关键词: Address; Adult; Affect; Age; Amyotrophic Lateral Sclerosis; Arizona; Autopsy; Behavior assessment; Behavioral; Behavioral Symptoms; Blood; Boston; Brain; Caring; Cells; Cessation of life; Clinical; Clinical Data; Clinical Management; Clinical assessments; Cognitive; Cohort Studies; Collaborations; Collection; Consensus; Country; DNA Library; Data; Development; Diagnosis; Disease; Disease Progression; Documentation; Enrollment; Environmental Risk Factor; Etiology; Freezing; Functional disorder; Funding; Future; Gene Mutation; Generations; Genetic; Genetic Polymorphism; Genetic Risk; Genomics; Health; Healthcare Systems; High Prevalence; Human; Impaired cognition; Incidence; Institution; Laboratories; Link; Low Prevalence; Medical Informatics; Methods; Military Personnel; Modeling; Monitor; Neuraxis; Neurodegenerative Disorders; Neurologic; Paralysed; Patients; Persons; Population; Positioning Attribute; Prevalence; Proteomics; Qualifying; Recovery; Registries; Relative (related person); Research; Research Personnel; Research Support; Resources; Risk; Sampling; Services; Site; Spinal Cord; Telephone; Telephone Interviews; Time; Tissue Banking; Tissue Banks; Tissue Donations; Tissue Donors; Tissue Sample; Tissues; Veterans; Veterans Hospitals; behavioral impairment; biobank; cohort; cost; data management; disability; effective therapy; follow-up; health administration; improved; mouse model; neuropathology; operation; outreach program; prospective; public health relevance; research and development; screening; success; tissue processing

DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is an adult onset, rapidly fatal, neurodegenerative disease of unknown etiology. The relatively low prevalence (6-8 cases per 100,000) and short survival time (3-5 years) of patients with ALS present impediments to establishing sizeable national cohorts needed for research. 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. Studies have indicated a higher prevalence of ALS among veteran groups than among civilians. Because of this, the Department of Veterans Affairs (VA) started the VA Biorepository Brain Bank (VABBB) to support ALS research. The VABBB is presently the only national prospective cohort study and CNS tissue bank that is enrolling and conducting ongoing follow-up on veteran enrollees with ALS. The VABBB is a multi-site collaboration among VA Boston Healthcare System (VABHS), the Southern Arizona Core Tissue Laboratory (SACTL) at the Southern Arizona VA Healthcare System (SAVAHCS), and the VISN-1 Neuropathology Laboratory at the Edith Nourse Rogers Memorial Veterans Hospital in Bedford, MA. The VABBB utilizes the strengths across the Boston/Bedford and Tucson sites in enrollment, tissue banking operations, neuropathological diagnosis, medical informatics and data management. The VABBB cohort is notable for its size, the amount and quality of CNS tissue and clinical data available, and especially for the relatively long duration and slow disease progression in the cohort. Tissue and clinical data from the VABBB are available for distribution to qualified researchers. Recent studies have noted the importance of better classifying patients according to the relative salience of the cognitive/behavioral symptoms in ALS in order to improve our understanding of ALS pathophysiology. Accordingly, we seek to enhance our characterization of the VABBB cohort by prospectively screening for cognitive and behavioral impairment. Over the next four years the specific aims are: 1) To continue, and enhance, the VABBB as the only national ALS prospective cohort study and CNS tissue bank supporting ALS research in the U.S.; and 2) To characterize cognitive and behavioral dysfunction in our cohort to support research on the pathophysiology and clinical management of ALS. For Specific Aim 1, the VABBB will continue to follow the present cohort of 127 veterans, enroll 140 new eligible veteran tissue donors, and continuously improve our overall methods. This will be accomplished through an outreach program across VAs nationwide, collaboration with other institutions, and improvement in our clinical assessment and CNS-tissue banking methods. The VABBB will also enhance its already robust national CNS tissue recovery network. This will involve 1) thorough neuropathological analysis of all brains and spinal cords with rigorous semi-quantitative documentation of the histopathological, immunohistochemical, and anatomical findings; 2) collaborations with investigators to assess tissue for genetic mutations and polymorphisms; 3) generation of a larger and more diverse collection of CNS tissue from Veteran controls; and 4) development of a national outreach program to further promote the use of VABBB tissue and data by ALS researchers. For Specific Aim 2, a cognitive/behavioral telephone assessment will be added to improve cohort characterization and add value to future CNS tissue collection. These improvements will facilitate clinicopathological studies of ALS by correlating these cognitive/behavioral assessments with histopathological, immunohistochemical, and genetic data. The availability of high quality fixed and frozen CNS tissue and data from this well characterized cohort is an important resource to facilitate research into genetic and environmental risk factors and clinical pathological relationships in ALS.

描述（由申请人提供）： 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。 ALS 患者的患病率相对较低（每 100,000 人中有 6-8 例）且生存时间较短（3-5 年），这阻碍了建立研究所需的大规模全国队列。对于开发收集中枢神经系统 (CNS) 组织样本并标注生物医学 ALS 研究必需的临床信息的生物样本库来说尤其如此。尽管已经开发了许多小鼠模型来研究 ALS，但这些模型是有限的，并且 ALS 基因组和蛋白质组研究对研究质量的人类中枢神经系统组织的需求至关重要。研究表明，退伍军人群体中 ALS 的患病率高于平民。因此，退伍军人事务部 (VA) 启动了 VA 生物储存脑库 (VABBB) 以支持 ALS 研究。 VABBB 是目前唯一一个正在招募患有 ALS 的退伍军人并对其进行持续随访的国家前瞻性队列研究和 CNS 组织库。 VABBB 是 VA 波士顿医疗系统 (VABHS)、南亚利桑那州 VA 医疗系统 (SAVAHCS) 的南亚利桑那州核心组织实验室 (SACTL) 和 Edith Nourse Rogers 纪念馆的 VISN-1 神经病理学实验室之间的多站点合作马萨诸塞州贝德福德的退伍军人医院。 VABBB 利用波士顿/贝德福德和图森站点在登记、组织库操作、神经病理学诊断、医学信息学和数据方面的优势 管理。 VABBB 队列因其规模、中枢神经系统组织的数量和质量以及可用的临床数据而引人注目，特别是该队列的持续时间相对较长且疾病进展缓慢。来自 VABBB 的组织和临床数据可分发给合格的研究人员。最近的研究指出了根据 ALS 认知/行为症状的相对显着性对患者进行更好分类的重要性，以提高我们对 ALS 病理生理学的理解。因此，我们寻求通过前瞻性筛查认知和行为障碍来增强对 VABBB 队列的表征。未来四年的具体目标是： 1) 继续并加强 VABBB 作为美国唯一支持 ALS 研究的国家 ALS 前瞻性队列研究和 CNS 组织库； 2) 表征我们队列中的认知和行为功能障碍，以支持病理生理学研究 以及 ALS 的临床管理。对于具体目标 1，VABBB 将继续跟踪现有的 127 名退伍军人队列，招募 140 名新的合格退伍军人组织捐献者，并不断改进我们的整体方法。这将通过全国 VA 的推广计划、与其他机构的合作以及改进我们的临床评估和 CNS 组织库方法来实现。 VABBB 还将加强其已经强大的国家中枢神经系统组织恢复网络。这将涉及：1）对所有大脑和脊髓进行彻底的神经病理学分析，并对组织病理学、免疫组织化学和解剖学发现进行严格的半定量记录； 2）与研究人员合作评估组织的基因突变和多态性； 3) 从退伍军人对照中产生更大、更多样化的 CNS 组织集合； 4) 制定国家推广计划，以进一步促进 ALS 研究人员使用 VABBB 组织和数据。对于具体目标 2，认知/行为电话评估 将添加以改善队列特征并为未来中枢神经系统组织收集增加价值。这些 通过关联这些认知/行为，改进将促进 ALS 的临床病理学研究 使用组织病理学、免疫组织化学和遗传数据进行评估。高质量固定和冷冻 CNS 组织以及来自这个特征明确的队列的数据的可用性是促进 ALS 遗传和环境风险因素以及临床病理关系研究的重要资源。