HABS-HD - Project 2

HABS-HD - 项目 2

• 批准号: 10708895
• 负责人: Sid E O'Bryant
• 金额: $ 41.28万
• 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/10708895
• 关键词: Adult; African American population; Age; Age of Onset; Alzheimer' s Disease; Alzheimer' s disease related dementia; Amyloid; Anti-Inflammatory Agents; Biological Markers; Blood Vessels; Clinical; Clinical Trials; Cognition; Collaborations; Data; Disease Outcome; Elderly; Ethnic Origin; Ethnic Population; 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; Pharmaceutical Preparations; Population; Population Heterogeneity; Prediction of Response to Therapy; Prevalence; Proteomics; Race; 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 difference; racial population; 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阿尔茨海默氏病（AD） +阿尔茨海默氏病（ADRD）的里程碑1.i 实施里程碑明确呼吁测试“多种病因的早期机械途径 可以考虑广告/ADRD的健康差异”。与广告有关的美国存在重大健康差异 非裔美国人（AAS）目前遭受广告/ADRD的最高烧伤，而西班牙裔（其中65％是 到20602 年龄较小的认知损失。尽管有这些因素，AAS和MAS仍然不足 广告研究。实际上，美国国家老化研究所（NIA）阿尔茨海默氏病中心的参与者中有83％ （ADC）和90％的阿尔茨海默氏病神经影像学计划（ADNI）7是非西班牙裔白人（NHW）。 此外，代表机械途径（淀粉样蛋白[a]，tau [t]， 神经变性[n]）主导当前的临床试验景观，几乎完全建立在 大多数医疗合并症都被筛选的NHW。然而，新兴数据证明了 AT（N）定义的生物标志物的种族/种族差异，因此该框架适用于AAS MAS仍然未知，这是项目1的重点。AAS和MAS也遭受了较重的燃烧 血管，代谢和炎症（VMI）因素，每个因素都有与AD的良好联系，包括 在（n）生物标志物。因此，VMI因素可能是目标的“早期机械途径”，有助于 如果不包含已知的人群，无法理解的广告健康分布 最高的燃烧。项目2将评估VMI因素对流行率的影响 和AT（n）定义的生物标志物的轨迹和三个最大种族/族裔的认知损失 美国的组目标1：检查VMI因素对认知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：检查 AT（N）定义生物标志物的存在，序列和轨迹的VMI因素 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 APOEε4基因型和其他与VMI相关的AD遗传标记的种族/种族特异性影响 - AT（n） 定义的生物标志物。 AIM 4（项目 - 项目互动）：与项目1和3合作开发一个 对AT（N）定义的生物标志物的全面理解。探索目标5： 将VMI数据和VMI - AT（n）相互作用数据与其他大规模计划（例如ADNI）进行比较 LEAD，ADC，WHICAP，SOL/INCA，ABC-DS，MARKVCID的确和其他人。