Omics Core Abstract The Omics Core (Core E), led by Drs. Sid O’Bryant and Mark Mapstone will use advanced methods to conduct state of the art quantitation of fluid-based biomarkers representing all levels of systems biology; from the genome to the metabolome for use in the proposed projects and to share with the broader scientific community. We will derive genomic, transcriptomic, proteomic, and metabolomic information from peripheral blood and cerebrospinal fluid (CSF) collected from our participants as part of our established clinical protocol. Peripheral blood is an accessible matrix with only minor risks associated with collection and would be preferred for translational applications, while CSF is a CNS-specific matrix with high specificity for CNS disorders like AD in DS. We will employ targeted approaches to quantify known markers from these matrices based on our preliminary work and we will use untargeted methods to quantify a variety of other potential markers. This combined approach will provide the highest likelihood of capturing the most valid and reliable fluid-based biomarkers and a rich dataset for new biomarker discovery by our group and other qualified groups around the world. The Core is represented by world class scientists with expertise in genomics and transcriptomics (Lee, Kamboh, Feingold, Cruchaga, Harari), epigenomics (Tycko), proteomics (O’Bryant, Fagan), and metabolomics (Mapstone, Cheema, Macciardi).