VA Biorepository Brain Bank

描述（由申请人提供）： 肌萎缩侧索硬化症（ALS）是一种病因不明的成人发病、迅速致死的神经退行性疾病。ALS患者相对较低的患病率（每10万人6-8例）和较短的生存时间（3-5年）阻碍了建立研究所需的大规模国家队列。这对于开发生物储存库的努力尤其如此，所述生物储存库收集注释有生物医学ALS研究所必需的临床信息的中枢神经系统（CNS）组织样本。虽然已经开发了许多小鼠模型来研究ALS，但这些模型是有限的，并且对于用于ALS的基因组和蛋白质组学研究的研究质量的人类CNS组织的需求是至关重要的。研究表明，退伍军人群体中ALS的患病率高于平民。正因为如此，退伍军人事务部（VA）启动了VA生物储备脑库（VABBB）来支持ALS研究。VABBB是目前唯一的国家前瞻性队列研究和中枢神经系统组织库，正在招募和进行持续随访的退伍军人登记与ALS。VABBB是VA波士顿医疗保健系统（VABHS）、南亚利桑那州VA医疗保健系统（SAVAHCS）的南亚利桑那州核心组织实验室（SACTL）和马萨诸塞州贝德福德伊迪丝·诺斯·罗杰斯纪念退伍军人医院的VISN-1神经病理学实验室之间的多中心合作。VABBB利用波士顿/贝德福德和图森研究中心在入组、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、CNS组织的数量和质量以及可用的临床数据而引人注目，尤其是队列中相对较长的持续时间和缓慢的疾病进展。VABBB的组织和临床数据可分发给合格的研究人员。最近的研究已经注意到根据ALS中认知/行为症状的相对显著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，我们寻求通过前瞻性筛查认知和行为障碍来增强我们对VABBB队列的表征。在接下来的四年里，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;和2）描述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 和ALS的临床管理。对于具体目标1，VABBB将继续跟踪目前的127名退伍军人，招募140名新的合格退伍军人组织供体，并不断改进我们的整体方法。这将通过全国VA的外展计划，与其他机构的合作，以及我们的临床评估和CNS组织库方法的改进来实现。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结果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）从退伍军人对照组中产生更大和更多样化的CNS组织;和4）发展一个国家推广计划，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 将增加，以改善队列表征，并增加未来CNS组织采集的价值。这些 这些改善将通过将这些认知/行为相关性来促进ALS的临床病理学研究。 组织病理学、免疫组织化学和遗传学数据评估。高质量的固定和冷冻CNS组织的可用性和来自该良好表征的队列的数据是促进ALS的遗传和环境风险因素以及临床病理关系的研究的重要资源。

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.