HABS-HD - Project 1

HABS-HD项目1摘要 2018年的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 (AD)是为了推进临床试验事实上，第一种降淀粉样蛋白药物（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 来自非西班牙裔白色（NHW）个体的临床研究。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%是西班牙裔 (65%是墨西哥裔美国人[MA]）。AA目前AD和AD相关疾病的负担最高 痴呆症（ADRD），而西班牙裔将在2060年前经历AD/ADRD的最大增长。因此，我们认为， 迫切需要了解AT（N）框架的相关性，以及相关的基于生物标记的 43%的美国人口使用的药物。此外，虽然有大量的文献表明， 成年早期的因素对老年痴呆症的风险有重大影响，我们对老年痴呆症的理解是， 这些因素对AD基本生物标志物的最早体征和进展模式的影响 在不同的社区中仍然是未知的。健康与老龄化大脑研究-健康差异 （HABS-HD）是第一个大规模的，以社区为基础的项目，同时研究每一个AT（N）定义 在美国三个最流行的种族/民族群体中，AAs，MA和 NHWs。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的新型AD治疗和预防策略。项目1将测试 假设AT（N）的时间、顺序、轨迹、进展和认知影响 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 非裔美国人、墨西哥裔美国人和非西班牙裔白人。目的2：检查血液的效用- 用于筛选后续PET和/或基于MRI的AT（N）确证性诊断的生物标志物谱 墨西哥裔美国人，非洲裔美国人和非西班牙裔白人的方法。目标3：审查影响 在非裔美国人、墨西哥裔美国人和非裔美国人中， 西班牙裔白人目标4：与项目2和项目3合作，全面了解 不同生物学、麻烦组和社会文化因素对AT（N）定义的生物标志物的影响 人口。探索性目标5：比较HABS-HD的AT（N）生物标志物数据与其他大型 规模计划，如ADNI、LEADS、ADCs、WHICAP、SOL/印加、ABC-DS、New IDEAS等。

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.