Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat2)

About This Grant

PROJECT SUMMARY The multi-partner consortium to expand dementia research in Latin America 2 (ReDLat2) seeks to address critical gaps in Latinos with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD). Latinos have been underrepresented in research despite being the most significant and fastest-growing minority in the United States (US). The project's long-term goal is to develop tailored models to assess and address the multimodal diversity across socioeconomic, genetic, and brain levels in Latino populations from Argentina, Brazil, Chile, Colombia, Mexico, and Peru compared to US participants. This multimodal approach will integrate data from 3,000 new participants (750 with AD, 750 with FTLD, 1,500 controls) with preexisting data (ReDLat1, N=3,000) via UCSF's strategic partners, and with secondary data from three other ReDLat-related R01s. Specific Aim 1 investigates how socioeconomic disparities affect dementia phenotypes across different data modalities, such as clinical, cognitive, and neuroimaging data. Aim 1 will include Latin America and the US participants, hypothesizing that adverse socioeconomic conditions (measured with social determinants of health, socioeconomic status, and inequality metrics) influence the multimodal phenotypes in aging and dementia. Aim 2 seeks to identify rare and common genetic variants contributing to AD and FTLD within large families and case-control cohorts across Latin America. Whole genome sequencing with short and long reads will be used to discover novel genes and test a newly developed Latino-specific polygenic risk score (PRS). Aim 3 will develop models to evaluate participants' brain age gap (BAG), utilizing computational semiempirical modeling and generative approaches that consider socioeconomic factors and genetic risks. The hypothesis is that these models will show differences in accelerated aging among Latinos compared to non-Latinos, modulated by socioeconomic and genetic risks. The methodology involves a comprehensive and harmonized data collection strategy encompassing clinical assessments, plasma biomarkers, cognitive testing, genomic analysis, and neuroimaging. These participants will be drawn from Latin America and the US, focusing on those socioeconomically disadvantaged and with familial antecedents of dementia. Whole genome sequencing will identify genetic markers and variants associated with dementia, complemented with plasma biomarkers (Aβ40, Aβ42, p-tau proteins, and others). The study will create a unique dataset that includes genetic data and measures of socioeconomic disparities from underrepresented groups, which will be invaluable for numerous scientific inquiries. This project is poised to transform the understanding of dementia in Latinos by integrating genetic and environmental factors, thus facilitating the development of targeted interventions and treatments that are culturally and genetically appropriate. The success of this initiative could lead to broader applications in other minority populations, ultimately contributing to more personalized and effective healthcare solutions.