HABS-HD - Project 2

HABS-HD - 项目 2

• 批准号: 10493853
• 负责人: Meredith Nicole Braskie
• 金额: $ 45.51万
• 依托单位: UNIVERSITY OF NORTH TEXAS HLTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10493853
• 关键词: Adult; African American population; Age; Age of Onset; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Biological Markers; Blood Vessels; Clinical; Clinical Trials; Cognition; Data; Disease Outcome; Disease Progression; Ethnic group; Etiology; Genetic Markers; Genotype; Health; Hispanic Populations; Impaired cognition; Inflammation; Inflammatory; Link; Medical; Metabolic; Mexican Americans; National Institute on Aging; Nerve Degeneration; Not Hispanic or Latino; Outcome; Participant; Pathway interactions; Pattern; Population; Population Heterogeneity; Prediction of Response to Therapy; Prevalence; Proteomics; Research; Risk; TREM2 gene; Testing; Work; aging brain; apolipoprotein E-4; burden of illness; comorbidity; dementia risk; diabetic; ethnic difference; experience; health disparity; middle age; mild cognitive impairment; neuroimaging; patient subsets; racial and ethnic; tau Proteins; vascular factor

HABS-HD PROJECT 2 ABSTRACT Milestone 1.I of the NIA Alzheimer’s Disease (AD) + Alzheimer’s Disease-Related Dementias (ADRD) Implementation Milestones explicitly calls for testing “early mechanistic pathways of multiple etiologies that may account for AD/ADRD health disparities”. Significant health disparities exist in the U.S. related to AD with African Americans (AAs) currently suffering the highest burden of AD/ADRD while Hispanics (65% of which are Mexican American [MA]) will experience the greatest increase in disease burden by 20602. MAs also develop cognitive loss at significantly younger ages. Despite these factors, AAs and MAs remain underrepresented in AD research. In fact, 83% of participants in the National Institute of Aging (NIA) Alzheimer’s Disease Centers (ADC) and 90% of the Alzheimer’s Disease Neuroimaging Initiative (ADNI)7 are non-Hispanic white (NHW). Additionally, the 2018 AT(N) framework, which represents the mechanistic pathways (amyloid [A], tau [T], neurodegeneration [N]) dominating the current clinical trial landscape, was built almost entirely on data from NHWs who are screened out for most medical comorbidities. Nevertheless, emerging data demonstrates racial/ethnic differences in AT(N) defined biomarkers and, therefore, the applicability of the framework to AAs and MAs remains unknown, which is the focus of Project 1. AAs and MAs also suffer a heavier burden of vascular, metabolic and inflammatory (VMI) factors, each of which have well-established links to AD, including AT(N) biomarkers. Therefore, VMI factors may be targetable “early mechanistic pathways” that contribute to AD health disparities that cannot be understood without inclusion of populations known to experience the highest burden from them. Project 2 will evaluate the impact of VMI factors on the prevalence, sequence and trajectories of AT(N) defined biomarkers and cognitive loss among the three largest racial/ethnic groups in the U.S. Aim 1: Examine the impact of VMI factors on the presence and progression of cognitive loss among African Americans, Mexican Americans, and non-Hispanic whites. Aim 2: Examine the impact of VMI factors on the presence, sequence and trajectories of AT(N) defined biomarkers among African Americans, Mexican Americans, and non-Hispanic whites. Aim 3: Determine if VMI factors explain the racial/ethnic specific impact of APOEε4 genotype - and other VMI-related AD genetic markers - on AT(N) defined biomarkers. Aim 4 (Project – Project Interactions): Collaborate with Projects 1 and 3 to develop a comprehensive understanding of AT(N) defined biomarkers across diverse populations. Exploratory Aim 5: Compare VMI data and VMI – AT(N) interaction data with that from other large-scale initiatives such as ADNI, LEADS, ADCs, WHICAP, SOL/INCA, ABC-DS, MarkVCID, INDEED, and others.

HABS-HD项目2摘要 NIA阿尔茨海默病（AD）+阿尔茨海默病相关痴呆（ADRD）的里程碑1.I 实施里程碑明确要求测试“多种病因的早期机制途径， 可能导致AD/ADRD健康差异”。美国存在与AD相关的显著健康差异， 非裔美国人（AAs）目前遭受AD/ADRD的最高负担，而西班牙裔美国人（65%） 墨西哥裔美国人[MA]）将在20602年经历最大的疾病负担增长。MA还开发 认知能力丧失的年龄要小得多。尽管存在这些因素，但在2009年， AD研究。事实上，在国家老龄化研究所（NIA）阿尔茨海默病中心的参与者中， (ADC)90%的阿尔茨海默病神经影像学倡议（ADNI）7是非西班牙裔白色（NHW）。 此外，2018年AT（N）框架，代表了机械途径（淀粉样蛋白[A]，tau [T]， 神经变性[N]）主导当前临床试验的景观，几乎完全建立在来自 筛查出大多数医学合并症的NHW。然而，新的数据表明， AT（N）定义的生物标志物的种族/民族差异，因此，框架对AA的适用性 而MAs仍然未知，这是项目1的重点。AA和MA也承受着更重的负担， 血管、代谢和炎症（VMI）因素，其中每一个都与AD有明确的联系，包括 AT（N）生物标志物。因此，VMI因素可能是有针对性的“早期机制途径”，有助于 如果不包括已知经历过AD的人群，就无法理解AD健康差异。 最大的负担。项目2将评估VMI因素对患病率、序列、 AT（N）定义的生物标志物和认知丧失的轨迹， 目的1：检查VMI因素对认知障碍的存在和进展的影响。 非裔美国人，墨西哥裔美国人和非西班牙裔白人的损失。目标2：审查 VMI因素对非洲人AT（N）定义的生物标志物的存在、序列和轨迹的影响 美国人，墨西哥裔美国人和非西班牙裔白人。目标3：确定VMI因素是否解释了 APOEε4基因型和其他VMI相关AD遗传标记物对AT（N）的种族/种族特异性影响 确定的生物标志物。目标4（项目-项目互动）：与项目1和3合作， 全面了解不同人群中AT（N）定义的生物标志物。探索性目标5： 将VMI数据和VMI-AT（N）交互数据与其他大规模计划（如ADNI）的数据进行比较， LEADS、ADC、WHICAP、SOL/印加、ABC-DS、MarkVCID、INDEED等。