Understanding Alzheimer disease heterogeneity in Hispanic populations.

了解西班牙裔人群中阿尔茨海默病的异质性。

• 批准号: 10449014
• 负责人: Jorge Jesus Llibre-Guerra
• 金额: $ 10.22万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10449014
• 关键词: Accounting; Address; Admixture; Age; Age of Onset; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American; Amyloid beta-42; Area; Argentina; Award; Biological Markers; Brazil; Caribbean Hispanic; Caribbean region; Central American; Clinical; Clinical Research; Cognitive; Colombia; Cultural Diversity; Data; Data Set; Dementia; Development; Diagnosis; Disease; Disease Progression; Education; Elderly; Employment; Enrollment; Environment; Environmental Risk Factor; Epidemiology; Epigenetic Process; Ethnic group; European; Frequencies; Functional disorder; Future; Genetic; Genetic Determinism; Genetic Research; Goals; Health and Retirement Study; Hispanic; Hispanic Populations; Inflammation; Inherited; Intervention; K-Series Research Career Programs; Knowledge; Latin America; Life Cycle Stages; Life Style; Life course epidemiology; Measures; Mediating; Mentors; Mexico; Molecular Analysis; Molecular Genetics; Neurocognitive; Not Hispanic or Latino; Onset of illness; Other Genetics; Participant; Pathology; Pathway interactions; Phenotype; Population; Population Heterogeneity; Population Study; Prevalence; Prevention; Prevention strategy; Prognosis; Recording of previous events; Reporting; Research; Research Personnel; Risk; Risk Factors; Role; Scientist; Severity of illness; Social Sciences; South American; Statistical Methods; Subgroup; Training; Training Programs; Translating; Universities; Vascular Diseases; Washington; Work; amyloid imaging; apolipoprotein E-4; behavioral neurology; biomarker signature; cardiovascular risk factor; career; clinical biomarkers; cognitive performance; cohort; comorbidity; design; disease disparity; disease heterogeneity; effective intervention; epidemiology study; ethnic diversity; familial Alzheimer disease; gene environment interaction; genetic architecture; genetic epidemiology; genetic variant; health disparity; hispanic community; longitudinal analysis; low socioeconomic status; molecular marker; multimodality; neuroimaging; neuroimaging marker; novel; prevent; progression marker; rate of change; skills; social; social disparities; social health determinants; β-amyloid burden

PROJECT ABSTRACT: This proposal seeks to understand the impact of genetic and social risk factors on Alzheimer's disease (AD) age at onset, disease progression and biomarkers trajectories in Hispanic populations. Under the guidance of primary mentor Dr. Randall J. Bateman, the training and research plan will build upon Dr. Jorge Libre's expertise in behavioral neurology and epidemiology of AD in Hispanic populations to prepare him for an independent career that integrates genetics, social science, and life course epidemiology into the study of AD. Dr.Llibre will pursue a mentored research scientist program of training at Washington University, that will advance his knowledge and skills in (1) enhanced knowledge of the genetic architecture of Alzheimer's disease, genetics epidemiology and advances in the analysis of molecular genetic data, (2) statistical methods for longitudinal analysis, (3) clinical and biomarkers assessments of AD and (4) use large data for the study of AD. These are the areas needed to further develop his expertise and become a successful, independent investigator. The research proposed in this application was designed to significantly contribute to the field of AD in Hispanics populations. The research plan will capitalize on deeply phenotype cohorts and large populations studies including Caribbean-Hispanics (10/66 study, Caribbean American Dementia and Aging Study [CADAS], Dominantly Inherited Alzheimer's Network [DIAN]), Central and South American (10/66 study, DIAN) and Hispanics living in the US (US-Health and Retirement study [HRS], DIAN), which may provide a unique understanding of disease onset, progression, and biomarker rate of chance in different populations subgroups. Furthermore, we will explore AD trajectories in Hispanics with Dominantly Inherited AD (DIAD) and sporadic AD (sAD), which may provide a full spectrum of AD in Hispanic populations. The proposed datasets include detailed information on education, employment histories, cardiovascular risk factors, rich neurocognitive assessments and biomarkers. DIAN recently received an Alzheimer Association award to study Familial AD in Hispanic populations by enrolling research participants from Latin America (Mexico, Colombia, Brazil Argentina), which Dr. Llibre will use on his K award and as the starting point for his eventual R01 application. The proposal will explore the influence of genetics and social disparities of health on age at onset, cognitive profiles, and biomarker trajectories in Hispanic populations. This research will begin to fill a critical gap in AD knowledge by uncovering novel genetic and gene by environment interactions pathways leading to dementia in Hispanic populations, of which Dr. Llibre will use to determine future areas of independent research in Hispanics. This evidence can help identify strategies most likely to reduce the population burden of AD in Hispanics populations, as well as the disparities therein.

项目摘要： 该提案旨在了解遗传和社会风险因素对阿尔茨海默病 (AD) 的影响 西班牙裔人群的发病年龄、疾病进展和生物标志物轨迹。在指导下 主要导师 Randall J. Bateman 博士，培训和研究计划将以 Jorge Libre 博士的专业知识为基础 在西班牙裔人群中获得行为神经学和 AD 流行病学博士学位，为他的独立研究做好准备 将遗传学、社会科学和生命历程流行病学整合到 AD 研究中的职业。利伯博士将 在华盛顿大学参加受指导的研究科学家培训计划，这将提高他的能力 (1) 增强对阿尔茨海默病遗传结构、遗传学的知识和技能 流行病学和分子遗传数据分析的进展，（2）纵向统计方法 分析，(3) AD 的临床和生物标志物评估，(4) 使用大数据进行 AD 研究。这些都是 需要进一步发展他的专业知识并成为一名成功的独立调查员的领域。 本申请中提出的研究旨在为 AD 领域做出重大贡献 西班牙裔人口。该研究计划将利用深层表型队列和大量人群 研究包括加勒比-西班牙裔（10/66 研究、加勒比美洲痴呆症和老龄化研究 [CADAS]、 显性遗传性阿尔茨海默病网络 [DIAN]）、中美洲和南美洲（10/66 研究，DIAN）和 居住在美国的西班牙裔人（美国健康与退休研究 [HRS]，DIAN），这可能会提供独特的 了解不同人群亚组中疾病的发病、进展和生物标志物几率。 此外，我们将探讨显性遗传性 AD (DIAD) 和散发性 AD 的西班牙裔人群的 AD 轨迹 (sAD)，它可能提供西班牙裔人群中 AD 的全谱。拟议的数据集包括详细的 有关教育、工作经历、心血管危险因素、丰富的神经认知评估的信息 和生物标志物。 DIAN 最近因研究西班牙裔家族性阿尔茨海默病而荣获阿尔茨海默病协会奖 通过招募来自拉丁美洲（墨西哥、哥伦比亚、巴西、阿根廷）的研究参与者， Llibre 博士将利用他的 K 奖并作为他最终的 R01 申请的起点。 该提案将探讨遗传和健康的社会差异对发病年龄、认知能力的影响。 西班牙裔人群的概况和生物标志物轨迹。这项研究将开始填补AD领域的一个关键空白 通过发现新的遗传和基因通过环境相互作用途径导致痴呆症的知识 拉美裔人口，Llibre 博士将利用这些人口来确定拉美裔未来独立研究的领域。 这一证据可以帮助确定最有可能减轻西班牙裔 AD 人口负担的策略 人口以及其中的差异。