Understanding Alzheimer disease heterogeneity in Hispanic populations.

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。指导下 培训和研究计划将建立在豪尔赫·利伯雷博士的专业知识基础上 行为神经学和西班牙裔人群中AD的流行病学，为他进行独立的 将遗传学、社会科学和生命过程流行病学整合到AD研究中的职业。Llibre博士将 在华盛顿大学进行一项指导性的研究科学家培训计划，这将提高他的 知识和技能（1）提高阿尔茨海默病遗传结构的知识，遗传学 流行病学和分子遗传学数据分析的进展，（2）纵向统计方法 分析，（3）AD的临床和生物标志物评估和（4）使用大量数据进行AD研究。这些是 需要进一步发展他的专业知识，成为一名成功的独立调查员。 本申请中提出的研究旨在为以下领域的AD领域做出重大贡献： 西班牙裔人口。该研究计划将利用深入的表型队列和大型人群 研究包括加勒比-西班牙裔（10/66研究，加勒比裔美国人痴呆和衰老研究[CADAS]， 显性遗传阿尔茨海默病网络[DIAN]），中美洲和南美洲（10/66研究，DIAN）和 生活在美国的西班牙裔（美国健康和退休研究[HRS]，DIAN），这可能提供了一个独特的 了解不同人群亚组中疾病的发病、进展和生物标志物发生率。 此外，我们还将探讨显性遗传性AD（DIAD）和散发性AD的西班牙裔AD轨迹 (sAD)这可能提供了西班牙裔人群中AD的全谱。建议的数据集包括详细的 教育信息、就业史、心血管风险因素、丰富的神经认知评估 和生物标志物。DIAN最近获得了阿尔茨海默病协会的奖项，以研究西班牙裔的家族性AD 通过招募来自拉丁美洲（墨西哥、哥伦比亚、巴西和阿根廷）的研究参与者， 博士Llibre将使用他的K奖，并作为他最终R 01申请的起点。 该提案将探讨遗传学和健康的社会差异对发病年龄、认知能力、 西班牙裔人群中的生物标志物轨迹。这项研究将开始填补AD的一个关键空白 通过发现新的遗传和基因与环境相互作用途径， 西班牙裔人口，其中博士Llibre将用于确定西班牙裔独立研究的未来领域。 这些证据可以帮助确定最有可能减少西班牙裔AD人口负担的策略 人口，以及其中的差距。

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.