Biological heterogeneity in ADRD

摘要： 阿尔茨海默氏病和相关痴呆症（ADRD）代表了美国历史上的一场医疗危机， 人口继续老化。AD研究中心（ADRC）和神经生物银行（NBB），都资助 由美国国立卫生研究院，代表两个独立的网络都专注于促进和支持人类大脑的研究， 前者专注于ADRD在具有最深专业知识的良好特征的前瞻性队列中， ADRD神经病理学的基础设施，后者拥有最广泛的网络， 中心之间的协调、外展管道以及数据和组织共享机制。2017年ADC 专家组的建议包括多个侧重于ADRD神经病理学，包括开发 纳入代表性不足群体和非痴呆（对照）供体的机制， 增加当地社区参与大脑捐赠的参与度和机会， 加强ADRC和NBB网络之间的合作，以促进大脑捐赠和研究大脑 组织利用的科学家专注于ADRD。作为回应，成立了一个协会-NBB工作组， 探索满足这一需求的机会，从而形成一个试点方案，以测试其中一些 解决方案该提案旨在支持华盛顿大学开展这项试点研究，该研究有五个目标， 成功完成，将开发，实施和测试机制，在ADRC和NBB，以确定和 同意ADRD脑捐赠者，包括对照组，以全国协调的方式，从 同意的捐赠者通过使用优化的程序，以获得最高的组织质量，用于研究， 最先进的神经病理学检查，通过关键的供体元数据补充这些数据， 结构化的家庭访谈和医疗记录审查，以在整个社区共享这些去识别信息。 网络和美国各地的研究人员，并填补这些捐助者的数据和组织要求，根据 这个基础设施，以支持ADRD研究。这项试点研究一旦成功完成， 确定有效的机制/协议/管道，以支持人类大脑捐赠和研究， 最终有助于推动ADRD研究走向机制知识，改进诊断策略， 有效的治疗措施。

Abstract: Alzheimer's disease and related dementias (ADRD) represent a healthcare crisis of epic proportions as the US populations continues to age. The AD Research Centers (ADRC) and the NeuroBiobank (NBB), both funded by NIH, represent two separate networks both focused on promoting and supporting human brain research, the former focused on ADRD in well-characterized prospective cohorts with the deepest expertise and infrastructure for ADRD neuropathology, and the latter with the broadest network with well-established coordination across center, outreach pipelines, and data and tissue sharing mechanisms. The 2017 ADC Panel Recommendations included multiple focused on ADRD neuropathology, including developing mechanisms for inclusion of donors from underrepresented groups and non-demented (control) donors, increasing engagement with and opportunity for local communities to participate in brain donation, and enhancing collaborations across the ADRC and NBB networks to promote brain donation and research brain tissue utilization by scientists focused on ADRD. In response, an ADRC-NBB working group was established to explore opportunities to meet this need, resulting in formation of a pilot program to test some of these solutions. This proposal is for support of the UW site for this pilot study, which has five aims that, when successfully completed, will develop, implement, and test mechanisms across ADRC and NBB to identify and consent ADRD brain donors, including controls, in a coordinated manner nationally, to collect brains from consented donors who pass using procedures optimized for maximum tissue quality for research, to perform state-of-the-art neuropathological examination, to supplement this data with critical donor metadata through structured family interviews and medical records reviews, to share this deidentified information across the networks and with researchers across the US, and to fill data and tissue requests from these donors, based on this infrastructure, to support ADRD research. When successfully completed, this pilot study will have helped identify effective mechanisms/protocols/pipelines to support human brain donation and research that will ultimately help propel ADRD research toward mechanistic knowledge, improved diagnostic strategies, and effective therapeutic interventions.