HTORR High Priority Alzheimer's Disease and Related Dementias Human Biospecimen Resource

项目负责人/主要研究者（最后，第一，中间）：Bell，托马斯，J。 项目摘要： 开发有效的治疗或治愈多种疾病的方法需要转化研究， 与人类病理生理学直接相关。人类生物标本的使用在加速 通过为科学家提供直接的实验模型系统， 深入了解神经系统疾病的发病机制和治疗，包括阿尔茨海默病 和相关痴呆（AD/ADRD）解决AD/ADRD研究面临的几个复杂问题，包括 疾病的病因学以及改进的诊断和治疗策略的发展， 需要获得独特的人体组织资源， 来自指定队列的尸检AD/ADRD和正常对照供体的生物标本， 创造性和突破性研究的可重复实验结果。作为领先的人体组织供应商 对于生物医学研究界，国家疾病研究交流中心（NDRI）是501（c）（3），而不是- 一个营利性组织，始终处于协调生物标本采购的最前沿，以满足需求 推动科学实验方法的发展，促进前沿研究。30多年来，NDRI 已经收到了NIH的资金，用于对这一行政补充，人体组织和器官 研究资源（HTORR）资助号：U420DO11158。解决高优先级的研究领域 对于AD/ADRD，需要进行超出HTORR范围的尸检生物标本采集，NDRI 正在扩大他们的能力，以创建一个新的资源，AD/ADRD人类生物标本资源（ADBR）， 由3U42OD011158 - 30S1资助。在ADBR计划的第3年，NDRI继续遵循 ADBR咨询理事会关于生物标本采集和分发的建议， 与外地未满足或代表性不足的需求相一致的ADBR。对于目前继续实施 为了推进ADBR的发展，NDRI建议通过以下方式提高ADBR为PY4研究者提供的服务的成功率： 1)提供一个全国性的TSS网络，以提供各种死后患病和非患病的 2）回收和分配CNS组织以及其他感兴趣的组织和流体，以及 3)加强与生物医学研究界的沟通，招募新的ADBR研究人员， 评估AD/ADRD领域未满足的需求。与类似的资源相比，ADBR的广泛推广 努力和针对调查员需求的定制方法是该资源的主要区别。 总的来说，ADBR的目标和努力提供了一个动态的和协同的NIH资助的资源， 支持AD/ADRD研究社区的关键未满足的研究需求的进步。 相关性：作为痴呆症最常见的原因，AD是一种破坏性的、进行性的神经退行性疾病， 影响超过570万美国人的疾病（阿尔茨海默氏症协会等，2018）， 美国医疗保健系统以及护理人员的负担。到目前为止，还没有疾病修饰 为AD/ADRD患者提供治疗选择，使其成为研究界的高度优先事项。的 本提案的目的是提供来自死后AD/ADRD供体的生物标本，以及非 AD/ADRD人类生物标本资源（ADBR）的患病对照供体，适合支持 处理外地高度优先需求和关键问题的关键调查线。 OMB编号0925 - 0001/0002（修订版03/2020批准至02/28/2023）页码继续格式页码

Program Director/Principal Investigator (Last, First, Middle): Bell, Thomas, J. Project Summary: The development of effective treatments or cures for a wide range of diseases requires translational studies that are directly relevant to human pathophysiology. The use of human biospecimens plays a key role in accelerating scientific discoveries in neurological research by providing scientists with a direct experimental model system to advance understanding of pathogenesis and treatment of neurological disease, including Alzheimer’s disease and related dementias (AD/ADRD). To address several complex issues facing AD/ADRD research, including disease etiology as well as the development of improved diagnostics and treatment strategies, investigators require access to a unique human tissue resource that could provide rigorous and uniform collection of human biospecimens from defined cohorts of post mortem AD/ADRD and normal control donors to yield consistent and reproducible experimental results for inventive and groundbreaking studies. As a leading human tissue provider for the biomedical research community, the National Disease Research Interchange (NDRI) is a 501(c)(3), not- for-profit organization that remains at the forefront of coordinating biospecimen procurement to match the needs of advancing scientific experimental methodologies, enabling cutting-edge research. For over 30 years, NDRI has received NIH funding for the parent award to this administrative supplement, the Human Tissue and Organs for Research Resource (HTORR) Grant Number: U420DO11158. To address the high priority areas of research for AD/ADRD that require both post mortem biospecimen collection that are beyond the scope of HTORR, NDRI is expanding their capabilities to create a new resource, the AD/ADRD Human Biospecimen Resource (ADBR), funded by the active award 3U42OD011158-30S1. In Program Year 3 of the ADBR, NDRI continued to follow the recommendations from ADBR Advisory Council regarding biospecimen collection and distribution for the ADBR that align with an unmet or under represented need in the field. For the current proposal to continue the progression of the ADBR, NDRI proposes to enhance the success of ADBR’s service to investigators in PY4 by 1) providing a nationwide network of TSS to provide access to diverse post mortem diseased and non-diseased donor cohorts, 2) recovering and distributing CNS tissues in addition to other tissues and fluids of interest, and 3) enhancing communication to the biomedical research community to recruit new ADBR investigators and assess unmet needs of the AD/ADRD field. In contrast to similar resources, the ADBR’s extensive outreach efforts and customized approach to investigator needs are key differentiators for the resource. Collectively, the ADBR’s goals and efforts provides a dynamic and synergistic NIH-funded resource to support the advancement of critical unmet research needs for the AD/ADRD research community. Relevance: As the most common cause of dementia, AD is a devastating, progressive neurodegenerative disease that affects over 5.7 million Americans (Alzheimer’s Association et al, 2018) and has a significant burden on the US healthcare system as well as caregivers. As of yet, there are no disease-modifying treatment options available for AD/ADRD patients, making this a high priority for the research community. The objective of this proposal is to provide biospecimens from post mortem AD/ADRD donors, as well as non- diseased control donors for the AD/ADRD Human Biospecimen Resource (ADBR) that are suitable to support critical lines of investigation that address high priority needs and key issues in the field. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page