Understanding Alzheimer disease heterogeneity in Hispanic populations.

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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.