GENETICS CORE PROJECT SUMMARY/ABSTRACT This new application will build on our work of the two previous funding cycles in which we established the Human Genetics Core (HGC) as an essential part of the Columbia ADRC. The HGC provides a centralized resource for the organization and analysis of genetic data within the ADRC and projects affiliated with the ADRC at Columbia University by providing the full physical and intellectual infrastructure needed to coordinate genetic research efforts and provide a platform for investigators to create a better understanding of genotype-phenotype relationships for dementia and related endophenotypes. Specifically, the HGC will: (1) provide a genetic material repository to process, extract, store and distribute genetic material from patients and controls, and track the collection and usage of genetic material; (2) provide a genetic database for storage, handling, preparation and distribution of genomic data from ADRC subjects and large-scale datasets available to the ADRC; (3) provide a high-end cluster environment and analytical support in statistical genetics and bioinformatics to facilitate genomic data analysis; (4) provide genetic counseling to patients and their families participating in the ADRC and ADRC affiliated studies; and (5) extend the large-scale genomic data available on this ADRC sample (ie. GWAS, WGS/WES, eQTL maps), and comprehensively characterize subjects for genetic variation in the amyloid, tau, immune response, cholesterol and endosomal trafficking pathways. In line with our vision for precision medicine, this characterization will move us forward to i) provide investigators with a backbone for more targeted research informed by genetic background, ii) disentangle potential pathophysiologic heterogeneity in this cohort, and iii) explore a variety of critical questions addressing the Thematic Aim by integration with the extensive translational data generated by the Neuropathology, Biomarker and Neuroimmunology Cores.