HABS-HD - Project 1

HABS-HD项目1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) 最近获得了FDA的批准。然而，几乎所有支持框架本身的数据以及临床 试验来自对非西班牙裔白人(NHW)个人的临床研究。到2060年，美国将 成为主要的非白人，15%的人口是非洲裔美国人(AA)，27.5%的人口是西班牙裔 (其中65%是墨西哥裔美国人[MA])。AAS目前对AD和AD相关的负担最高 痴呆症(ADRD)，而拉美裔人到2060年将经历AD/ADRD的最大增长。因此， 迫切需要了解AT(N)框架和基于相关生物标记物的相关性 治疗，为43%的美国人口提供服务。此外，虽然有丰富的文献证明 成年早期的因素对晚年痴呆症风险有重大影响，我们对 这些因素对阿尔茨海默病基础标志物早期体征和进展模式的影响 在不同社区之间的关系在很大程度上仍然不为人知。健康与衰老大脑研究--健康差异 (HABS-HD)是第一个同时研究AT(N)定义的每个AT(N)的大规模、基于社区的项目 在美国最普遍的三个种族/民族中，成年后的生物标记物分别是AAS、MAS和MAS 保健品。HABS-HD的长期目标是建立针对特定人群的知情精准医学 符合NIA AD+ADRD里程碑1的新AD治疗和预防策略。项目1将测试 关于AT(N)的时间、顺序、轨迹、进展和认知影响的假设 生物标志物在非裔美国人、墨西哥裔美国人和非西班牙裔白人中有所不同。目标1： 检查AT(N)定义的生物标志物的纵向序列、轨迹、进展和认知影响 在非裔美国人、墨西哥裔美国人和非西班牙裔白人中。目标2：检查血液的效用- 用于筛选后续基于PET和/或MRI的AT(N)确认性诊断的生物标志物配置文件 方法在墨西哥裔美国人、非裔美国人和非西班牙裔白人中进行。目标3：检查影响 非裔美国人、墨西哥裔美国人和非美国人AT(N)定义的生物标志物上的基因组标记 西班牙裔白人。目标4：与项目2和项目3合作，全面了解 不同生物、暴露组和社会文化因素对AT(N)定义的生物标记物的影响 人口。探索性目标5：将HABS-HD的AT(N)生物标志物数据与其他大型矿体的AT(N)生物标志物数据进行比较 扩展计划，如ADNI、Leads、ADC、WHICAP、SOL/Inca、ABC-DS、New Ideas和其他。

HABS-HD PROJECT 1 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) recently received FDA approval. However, nearly all data supporting the framework itself, as well as the clinical trials, comes from clinic-based 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]). 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. 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. Additionally, while there is a wealth of literature demonstrating that factors in early adulthood have a significant impact on late-life dementia risk, our understanding of the impact of these factors on the earliest signs and progression patterns of the fundamental biomarkers of AD among diverse communities remains largely unknown. 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 across adulthood among the three most prevalent racial/ethnic groups in the U.S., AAs, MAs and NHWs. The long-term goal of HABS-HD is to establish population-specific informed precision medicine for novel AD treatment and prevention strategies in line with NIA AD+ADRD Milestone 1. Project 1 will test the hypothesis that the timing, sequence, trajectories, progression and cognitive impact of the AT(N) biomarkers differ among African Americans, Mexican Americans, and non-Hispanic whites. Aim 1: Examine the longitudinal sequence, trajectories, progression and cognitive impact of AT(N) defined biomarkers among African Americans, Mexican Americans, and non-Hispanic whites. Aim 2: Examine the utility of blood- based biomarker profiles for screening for subsequent PET and/or MRI-based AT(N) confirmatory diagnostic methods among Mexican Americans, African Americans, and non-Hispanic whites. Aim 3: Examine the impact of genomic markers on AT(N) defined biomarkers among African Americans, Mexican Americans and non- Hispanic whites. Aim 4: Collaborate with Projects 2 and 3 to develop a comprehensive understanding of the impact of diverse biological, exposome, and sociocultural factors on AT(N) defined biomarkers across diverse populations. Exploratory Aim 5: Compare AT(N) biomarker data from HABS-HD with that from other large- scale initiatives such as ADNI, LEADS, ADCs, WHICAP, SOL/INCA, ABC-DS, New IDEAS and others.