Administrative Core

摘要： “多种族人群中AD的中心连锁纵向外周生物标志物（CLEAR-AD）”是一项 来自多个学科的超过40名专家的U19协作应用程序，跨越13个机构，利用8个 NIH资助的独立队列，来自> 3，700人的> 7，000份大脑和> 13，000份血液样本，其中 将生成> 20，000个多组学数据点，并与> 48，000个协调的阿尔茨海默病整合 (AD)U19下的内表型我们的目标是发现、复制和验证下一代AD 血液多组学生物标记候选物，其代表脑中的分子扰动特征， 反映在死前神经影像学/脑脊液（CSF）和死后神经病理学表型中 这种复杂的疾病。我们的目标是发现中心连锁的外周分子特征（CLPMS）， 通过转录组，表观基因组，蛋白质组， 代谢组学/脂质组学数据生成，与现有的其他组学数据整合，并在匹配的 死后脑：死前血液样本（项目1=P1）;并表征其纵向动态 非西班牙裔白色（NHW）和非裔美国人的多样化、代表性不足人群（URP）中的特征 (AA)和拉丁美洲（LA）参与者（P2，P3）。我们希望能找出预测，诊断，预后和 具有机制见解的治疗性AD生物标志物;加强试验就绪的多种族 人口，并为研究界提供大量的资源，严格生成，复制和 验证的多组学生物标志物。为了实现这些目标，我们将利用和整合现有和未来的数据 阿尔茨海默病神经影像学倡议（ADNI），马约临床衰老研究（MCSA） 6个AD研究中心（ADRC）。行政核心（核心1：C1）将提供指导和监督 该计划的项目和核心（C2。组学和C3分析核心），并促进其执行。的 行政核心将通过以下方式实现计划目标：1）整合参与机构， 研究; 2）执行所有监管活动; 3）为学员建立多元化学者计划， URPs; 4）在U19内部实现沟通，推广和知识共享，以及相关计划， 整个研究界和公共利益相关者; 5）通过以下方式确保严谨性，可重复性和透明度 使所有的数据，算法和结果提供给研究界。具体目标 行政核心是：1）提供指导，监督，整合和促进所有U19的执行 在其指导委员会、外部咨询委员会和NIH的领导下实现目标（1a）;并执行所有 该计划的监管活动（1B）。2)通过建立一个U19来进行宣传和教育 多样性学者计划培训AA和LA科学家（2a）和两年一度的会议（2b）。3)共享数据 以开放科学的方式了解NIH批准的知识库，以提高透明度， 所有CLEAR-AD计划资产的可重复性和重复使用。

Summary Abstract: “Centrally-linked Longitudinal pEripheral biomARkers of AD (CLEAR-AD) in multi-ethnic populations” is a collaborative U19 application of >40 experts from multiple disciplines, across 13 institutions leveraging 8 independent NIH-funded cohorts of >7,000 brain and >13,000 blood samples from >3,700 individuals, in which >20,000 multi-omics data points will be generated and integrated with >48,000 harmonized Alzheimer’s disease (AD) endophenotypes under this U19. Our goal is to discover, replicate and validate the next-generation of AD blood multi-omics biomarker candidates that represent molecular perturbation signatures in the brain which are reflected in antemortem neuroimaging/cerebrospinal fluid (CSF) and post-mortem neuropathology phenotypes of this complex disease. We aim to discover centrally-linked peripheral molecular signatures (CLPMS) that can serve as future centrally-linked peripheral biomarkers (CLPBM) through transcriptome, epigenome, proteome, metabolome/lipidome data generation, integration with existing other -omics data and analysis in matched postmortem brain:antemortem blood samples (Project 1=P1); and to characterize their longitudinal dynamic profiles in non-Hispanic white (NHW) and diverse, underrepresented populations (URP) of African American (AA) and Latino American (LA) participants (P2, P3). We expect to identify predictive, diagnostic, prognostic and therapeutic AD biomarkers with mechanistic insights; to enhance biomarker research in trial-ready multi-ethnic populations and to provide the research community with a vast resource of rigorously generated, replicated and validated multi-omics biomarkers. To achieve these aims, we will utilize and integrate existing and future data and biospecimens from Alzheimer’s Disease Neuroimaging Initiative (ADNI), Mayo Clinic Study of Aging (MCSA) and 6 AD Research Centers (ADRCs). The Administrative Core (Core 1: C1) will provide direction and oversight to the projects and cores of this program (C2. Omics and C3. Analytic Cores) and facilitate their execution. The Administrative Core will achieve the program goals through 1) integration of the participating institutions and studies; 2) execution of all regulatory activities; 3) establishing a Diversity Scholars Program for trainees from URPs; 4) enabling communication, outreach and knowledge sharing within the U19, with related programs, the whole research community and public stakeholders; and 5) ensuring rigor, reproducibility and transparency by making all data, algorithms, and outcomes available to the research community. The Specific Aims for the Administrative Core are: 1) To provide direction, oversight, integration and facilitate execution of all U19 aims under the leadership of its Steering Committee, External Advisory Board and NIH (1a); and to execute all regulatory activities for the program (1b). 2) To perform outreach and education by establishing a U19 Diversity Scholars Program to train AA and LA scientists (2a) and bi-annual meetings (2b). 3) To share data and knowledge in an open-science fashion on NIH approved repositories to promote transparency, reproducibility and reuse of all CLEAR-AD program assets.