Health and Aging Brain among Latino Elders (HABLE-AT(N)) Study

项目摘要 2018年NIA -阿尔茨海默病协会研究框架[AT（N）]为阿尔茨海默病（AD）提供了一个 通过结合淀粉样蛋白（A）、tau（T）和 神经变性（N）。尽管这些生物标志物因种族/民族而异，但没有先前的工作 在墨西哥裔美国人中进行了系统的研究。考虑到（1）西班牙裔/拉丁裔预计将 到2060年，AD和阿尔茨海默病相关痴呆症（ADRD）的增长最快，以及（2） 墨西哥裔美国人是美国西班牙裔/拉丁裔人口的最大部分，迫切需要 研究这些生物标志物在这一代表性不足的群体中的患病率、进展和临床影响。 这项工作涉及国家阿尔茨海默病项目法案（NAPA），NIA AD和ADRD的目标 研究，以及AT（N）框架出版物强调的需求。 目前的研究团队由墨西哥裔美国人认知老化，神经影像学， (PET和MRI）、基于血液的生物标志物以及先进的统计建模。通过利用正在进行的 HABLE队列，基础设施和数据，我们将测试以下具体目标：目标1：检查 2018年AT（N）框架中脑标志物的患病率、进展和临床影响 墨西哥裔美国人社区目标二。检查的患病率，进展和临床影响， 2018年AT（N）框架的血液标志物在社区居住的墨西哥裔美国人中。目标3： 确定Aβ40、Aβ42、tau和NfL的血液生物标志物是否可用于筛查AT（N）定义的 临床前AD、前驱AD和AD痴呆，用于将墨西哥裔美国人纳入新型临床试验。 本研究具有重要意义，原因如下：（1）这是有史以来第一次大规模的多民族 AT（N）生物标志物的研究，鉴于美国的种族/民族构成，这一研究非常重要。 （2）这项工作直接涉及国家适应行动方案以及国家执行机构防治荒漠化/荒漠化和退化战略所规定的目标 科学;（3）它将确定种族特异性生物标志物轨迹是否合适，最后，（4）它将 生成数据和方法，以增加跨AT（N）定义的临床试验中西班牙裔的入组 AD的范围（一级、二级和三级预防）始于初级保健机构。

PROJECT SUMMARY The 2018 NIA - Alzheimer's Association Research Framework [AT(N)] for Alzheimer's Disease (AD) provides a biological context for studying AD by incorporating state-of-the art biomarkers of amyloid (A), tau (T) and neurodegeneration (N). Despite the fact that these biomarkers vary by race/ethnicity, no prior work has systematically examined them among Mexican Americans. Given that (1) Hispanic/Latinos are projected to experience the largest growth in AD and Alzheimer's Disease Related Dementias (ADRDs) by 2060 and (2) Mexican Americans are the largest segment of the U.S. Hispanic/Latino population, there is a pressing need to study prevalence, progression and clinical impact of these biomarkers among this underrepresented group. This work addresses goals of the National Alzheimer's Project Act (NAPA), NIA Milestones for AD and ADRD research, and needs highlighted by the AT(N) framework publication. The current research team consists of leading experts in Mexican American cognitive aging, neuroimaging (PET and MRI), blood-based biomarkers as well as advanced statistical modeling. By leveraging the ongoing HABLE cohort, infrastructure and data, we will test the following Specific Aims: Aim 1: Examine the prevalence, progression and clinical impact of cerebral markers of the 2018 AT(N) framework among community-dwelling Mexican Americans. Aim 2. Examine the prevalence, progression and clinical impact of blood markers of the 2018 AT(N) framework among community-dwelling Mexican Americans. Aim 3: To determine if blood-based biomarkers of Aβ40, Aβ42, tau and NfL can be used to screen for AT(N)-defined preclinical AD, prodromal AD and AD dementia for enrollment of Mexican Americans into novel clinical trials. The current study is highly significant for several reasons: (1) This is the first-ever large-scale multi-ethnic study of the AT(N) biomarkers, which is of tremendous importance given the racial/ethnic make-up of the U.S. population; (2) this work directly addresses goals set forth by NAPA as well NIA-Milestones for AD/ADRD science; (3) it will determine if ethnic-specific biomarker trajectories are appropriate and finally, (4) it will generate data and methods for increasing enrollment of Hispanics into clinical trials across the AT(N)-defined spectrum of AD (primary, secondary and tertiary prevention) beginning in primary care settings.