Understanding Alzheimer disease heterogeneity in Hispanic populations.

项目摘要： 这项建议旨在了解遗传和社会风险因素对阿尔茨海默病(AD)的影响 拉美裔人群的发病年龄、疾病进展和生物标记物轨迹。在…的指导下 主要导师兰德尔·J·贝特曼博士，培训和研究计划将建立在豪尔赫·利布雷博士的专业知识基础上 在行为神经学和西班牙裔人群中进行AD流行病学研究，为他的独立研究做好准备 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。利布雷博士会 在华盛顿大学进行有指导的研究科学家培训计划，这将促进他的 以下方面的知识和技能：(1)增强阿尔茨海默病的遗传结构、遗传学方面的知识 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)使用大量数据研究AD。这些是 这些领域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对AD领域做出重大贡献 拉美裔人口。这项研究计划将利用表型较深的人群和大量人群 研究包括加勒比-拉美裔(10/66研究，加勒比美国人痴呆症和老龄化研究[CADAS]， 主要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 居住在美国的拉美裔美国人(美国-健康和退休研究[HRS]，DIAN)，这可能提供一个独特的 了解不同人群亚组中疾病的发病、进展和生物标记物的机率。 此外，我们将探索具有显性遗传性AD(DIAD)和散发性AD的西班牙裔AD的发展轨迹 (SAD)，这可能提供西班牙裔人口中阿尔茨海默病的全谱。建议的数据集包括详细的 关于教育、就业史、心血管风险因素、丰富的神经认知评估的信息 和生物标记物。Dian最近获得了阿尔茨海默病协会奖，用于在西班牙裔研究家族性AD 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博士将在他的K奖上使用，并作为他最终的R01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 拉美裔人口中的概况和生物标记物轨迹。这项研究将开始填补AD的一个关键空白 通过发现导致痴呆的新的遗传和基因与环境相互作用的途径来获得知识 Llibre博士将利用其中的拉美裔人口来确定未来拉美裔独立研究的领域。 这一证据有助于确定最有可能减轻拉美裔AD人群负担的策略 人口问题，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.