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）： 肌萎缩性侧索硬化症（ALS）是一种成年的发作，迅速致命的病因神经退行性疾病。患病率相对较低（每100,000例6-8例）和ALS患者的短期生存时间（3 - 5年），这是建立研究所需的大量国家同类群体的障碍。对于开发收集中枢神经系统（CNS）组织样本的生物疗法的努力尤其如此，并用生物医学ALS研究必不可少的临床信息注释。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，并且对ALS中基因组和蛋白质组学研究的研究质量人中CNS组织的需求至关重要。研究表明，在退伍军人团体中，ALS的患病率要高于平民。因此，退伍军人事务部（VA）开始了VA Biorepository Brain Bank（VABBB）支持ALS研究。 VABBB目前是唯一的国家前瞻性队列研究，也是中枢神经系统组织库，该研究正在参加和对ALS的资深参与者进行持续的随访。 VABBB是VA波士顿医疗保健系统（VABHS），亚利桑那州南部核心组织实验室（SACTL）之间的多站点合作，位于亚利桑那州南部VA Healthcare System（SAVAHCS）和Visn-1神经病理学实验室的Edith Nourse Rogers Rogers Rogers Memorial Veterans Hospital in Bedford in Bedford，MA。 VABBB利用波士顿/贝德福德和图森地点的优势在招生，组织银行操作，神经病理学诊断，医学信息学和数据 管理。 VABBB队列的大小，CNS组织的数量和质量以及可用的临床数据，尤其是持续时间相对较长，并且疾病进展缓慢。来自VABBB的组织和临床数据可用于合格研究人员。最近的研究指出，根据ALS认知/行为症状的相对显着性更好地对患者进行分类的重要性，以提高我们对ALS病理生理学的理解。因此，我们试图通过前瞻性筛选认知和行为障碍来增强对VABBB队列的表征。在接下来的四年中，具体的目的是：1）继续并增强VABBB作为唯一的国家ALS前瞻性队列研究和中枢神经系统组织银行，支持美国的ALS研究； 2）在我们的队列中表征认知和行为功能障碍以支持有关病理生理学的研究 和ALS的临床管理。对于特定的目标1，VABBB将继续跟随目前的127名退伍军人队列，招募140个新的合格的退伍军人组织供体，并不断改善我们的整体方法。这将通过在全国范围内的VAS，与其他机构的合作以及我们的临床评估和中枢神经系统组织银行方法的改进来实现这一目标。 VABBB还将增强其已经强大的国家中枢神经系统组织回收网络。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，并具有严格的半定量文献记录组织病理学，免疫组织化学和解剖学发现； 2）与研究人员合作评估组织的基因突变和多态性； 3）从退伍军人控制中产生更大，更多样化的中枢神经系统组织； 4）制定国家外展计划，以进一步促进ALS研究人员使用VABBB组织和数据。对于特定目标2，认知/行为电话评估 将添加以提高队列表征并为未来的CNS组织收集增加价值。这些 改进将通过将这些认知/行为相关联促进ALS的临床病理研究 通过组织病理学，免疫组织化学和遗传数据进行评估。高质量固定和冷冻的中枢神经系统组织的可用性以及该特征良好的同类群体的数据是促进对ALS中遗传和环境危险因素以及临床病理关系研究的重要资源。