Center for Alzheimer's and Related Dementias (CARD): Collaboration with the Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat)

National Institute On Aging

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Abstract

Executive Summary The Multi-Partner Consortium to Expand Dementia Research in Latin America (ReDLat) represents a groundbreaking collaborative effort to understand the genetic architecture of Alzheimer's disease and related dementias (ADRD) in Latin American populations. This comprehensive project involves multi-site data collection across Latin America and Mexico, with advanced genomic and proteomic analyses being conducted through partnerships with leading research institutions. The project is currently processing samples through Psomagen for genotyping and is working to transition data management to the GP2 platform. The consortium has successfully established a robust research infrastructure spanning 10 sites in Latin America and 4 sites in Mexico, facilitating unprecedented genetic research capacity in the region. Through strategic partnerships with CARD (Center for Alzheimer's and Related Dementias) and other international collaborators, the project is generating comprehensive datasets that will advance our understanding of ADRD genetics in unique populations and contribute to the development of precision medicine approaches for these conditions. Project Summary Narrative This collaborative effort in Latin America focuses on understanding the genetics of Alzheimer's disease for ADRD genetics, clinical diagnostics, and data science. The project involves comprehensive sample collection across 10 sites in Latin America and 4 sites in Mexico, followed by whole genome sequencing and array-based genotyping. Long-read sequencing is being performed on a subset of cases to capture structural variants that may be missed by standard approaches in non-genetically-admixed populations. The ReDLat data has been analyzed and the first paper has been published, representing a significant milestone in this ongoing consortium project that integrates with GP2 and GNPC initiatives. Currently underway are analyses of brain proteomic quantitative trait loci (QTLs) that will result in a second major publication from the consortium. Milestones and Deliverables Completed Milestones: Successfully screened and recruited participants from various sites across Latin America (Status: Complete, On track) Completed computational genetic training for collaborators and trainees (Status: Complete) Published initial data descriptive paper (Status: Complete) Generated genetic data and uploaded to ADWB and Terra (AMP) platforms (Status: Complete) Completed data acquisition of proteomics in 676 AD and healthy control samples (Status: Complete) In Progress Milestones: Whole genome sequencing completion for all enrolled participants (Status: In progress, 4,155/6,000 samples complete, Minor concerns) Proteomic data generation and upload to GNPCv2 (Status: In progress, On track) Proteomic QTL analyses (Status: In progress) Data analysis projects (Status: In progress, On track) Upcoming Deliverables: Proteomic QTL research paper (Status: In development) Completion of remaining whole genome sequencing (1,845 samples remaining) Finalization of trainee visit program and analysis projects Current Project Status: The project is currently behind target due to sample processing delays, but samples are actively being processed at Psomagen and progressing steadily. The team is working to transition to GP2 space, though this is being delayed by data use agreement (DUA) requirements. Plans for proteomics analysis by Andy's team at CARD remain in progress, though the previous contract expired in April 2024. Research Network: Multi-site Latin American research network (10 sites in Latin America, 4 sites in Mexico) GP2 (Global Parkinson's Genetics Program) integration Global Neuroproteomic Consortium (GNPC) collaboration Commercial Partners: Psomagen (whole genome sequencing) Somalogic (proteomics analysis) Data Resources Whole genome sequencing data: Psomagen (4,155 samples completed) Proteomics data: GNPCv2 platform (https://www.neuroproteome.org/) Genetic data repository: ADWB and Terra (AMP) platforms Plasma samples: 676 AD/HC plasma samples currently incoming to GNPCv2