The Health & Aging Brain Study - Health Disparities (HABS-HD)

HABS-HD总体摘要 2018年AT(N)框架为该领域提供了阿尔茨海默病的第一个生物学概念化 (Ad)为推进临床试验的明确目的。事实上，第一种降低淀粉样蛋白的药物(Aducanumab) 现已获得FDA批准。然而，几乎所有的数据都支持框架本身，以及临床 试验来自对非西班牙裔白人(NHW)个人的研究。到2060年，美国将成为 主要是非白人，15%的人口是非洲裔美国人(AA)，27.5%的人是西班牙裔(65% 它们是墨西哥裔美国人[MA])。因此，迫切需要了解 AT(N)框架和相关的基于生物标记物的疗法，适用于43%的美国人口。目前的AAS AD和AD相关痴呆症(ADRD)的负担最重，而西班牙裔将经历最严重的 到2060年，AD/ADRDS增加。此外，NIA AD+ADRD实施里程碑1 明确要求检查“多种病因的早期机制途径”(1.i)、社会文化(1.i)和 在以社区为基础的队列中暴露(1亿)因素，包括尖端成像、液体、遗传和 不同人群中的其他生物标记物，以了解AD患者的健康差异。健康与衰老的大脑 研究-健康差异(HABS-HD)是第一个同时进行研究的大型社区项目 每个AT(N)定义的生物标志物，与NIA健康差异研究框架一致， 在美国最流行的三个种族/民族群体中，AA、MA和NHW。HABS-HD的目标 U19如下：目标1：收集影像、临床、生物和遗传数据，这些数据将导致 不同人群中最大的纵向队列，检查成年期的AT(N)生物标志物。目标2：实现 收集生命历程曝光(通过区域剥夺指数)以及社会文化数据，并研究如何 这些因素影响AT(N)生物标记物在不同人群中的时间、顺序和轨迹。目标 3：向全球科学界传播HABS-HD数据和样本。将制作HABS-HD数据 通过LONI提供，而生物流体样本将通过HABS-HD Omics Core提供。基因组学 数据将根据NIH/NIA的指导方针提供。HABS-HD的长期目标是建立人口- 为AD提供新的治疗和预防策略的特定知情精准医学。为了推进这一进程 为了实现这一目标，我们将开展以下项目：项目1)研究AT(N)的时间、顺序和轨迹 不同人群中的生物标志物；项目2)检查血管、代谢和炎症的影响 AT(N)生物标记物在不同人群中的时间、顺序和轨迹的因素；以及项目 3)考察曝光者(通过邻里劣势)和社会文化因素对 AT(N)生物标记物在不同人群中的时间、序列和轨迹。

HABS-HD OVERALL ABSTRACT The 2018 AT(N) framework provided the field with the first biological conceptualization of Alzheimer’s disease (AD) for the explicit purpose of advancing clinical trials. In fact, the first amyloid-lowering drug (aducanumab) has now received FDA clearance. However, nearly all data supporting the framework itself, as well as clinical trials, comes from research among non-Hispanic white (NHW) individuals. By 2060 the U.S. will become largely “non-white” with 15% of the population being African American (AA) and 27.5% being Hispanic (65% of which are Mexican American [MA]). Therefore, there is an urgent need to understand the relevance of the AT(N) framework, and associated biomarker-based therapeutics, for 43% of the U.S. population. AAs currently have the highest burden of AD and AD related dementias (ADRD) while Hispanics will experience the greatest increase in AD/ADRDs by 2060. Moreover, Milestone 1 of the NIA AD+ADRD Implementation Milestones explicitly call for examination of “early mechanistic pathways of multiple etiologies” (1.I), sociocultural (1.I) and exposome (1.B) factors among community-based cohorts that include cutting edge imaging, fluid, genetic and other biomarkers in diverse populations to understand health disparities in AD. The Health & Aging Brain Study – Health Disparities (HABS-HD) is the first large-scale, community-based project to simultaneously study each of the AT(N) defined biomarkers, in alignment with the NIA Health Disparities Research Framework, across the three most prevalent racial/ethnic groups in the U.S., AA, MA, and NHW. The Aims of the HABS-HD U19 are as follows: Aim 1: To collect imaging, clinical, biological and genetic data which will result in the largest longitudinal cohort of diverse populations that examines AT(N) biomarkers across adulthood. Aim 2: To collect life-course exposome (via the Area Deprivation Index), as well as sociocultural data and examine how these factors affect the timing, sequence and trajectories of AT(N) biomarkers among diverse populations. Aim 3: To disseminate HABS-HD data and samples to the global scientific community. HABS-HD data will be made available via LONI while biofluid samples will be made available through the HABS-HD Omics Core. Genomics data will be made available per NIH/NIA guidelines. The long-term goal of HABS-HD is to establish population- specific informed precision medicine for novel treatment and prevention strategies for AD. To advance this goal, we will conduct the following Projects: Project 1) Examine the timing, sequence and trajectories of AT(N) biomarkers across diverse populations; Project 2) Examine the impact of vascular, metabolic and inflammatory factors on the timing, sequence and trajectories of AT(N) biomarkers across diverse populations; and Project 3) Examine the impact of the exposome (via neighborhood disadvantage) and sociocultural factors on the timing, sequence and trajectories of AT(N) biomarkers across diverse populations.