BIOMARKER CORE ABSTRACT The Biomarker Core provides state-of-the-art biofluid processing, biobanking, and biomarker assays in blood and cerebrospinal fluid (CSF) to advance diagnostic, prognostic, mechanistic and therapeutics research for the Massachusetts ADRC (MADRC) and the broader ADRD research community. A particular interest of ours is the qualification of biomarkers that are fit-for-purpose to characterize heterogenous pathophysiological drivers of ADRD at group and individual participant levels. Through this we contribute to MADRC’s goal to understand disease and clinical progression as we integrate, analyze and interpret these data with all of MADRC's Cores' data. Our focus on precision and individual-specific biomarker profiling moves us closer to personalized medicine for ADRD and it enables research with broader inclusion of diverse peoples. In the course of this work, we train and mentor students, trainees, junior faculty and collaborators in the rapidly evolving use and growing value of biomarkers in ADRD research and clinical translation. Our Specific Aims are: Aim 1) Contribute to the diagnosis and biological characterization of ADRD for the MADRC and be a resource for biofluids, technologies and expertise in biomarkers research. We will bank blood and CSF constituents, measure amyloid, tau and neurodegeneration biomarkers in all MADRC specimens and share these biofluids and data for use by MADRC, collaborating and national and international ADRD research efforts. Aim 2) Discover new candidate biomarkers and develop new assays to fulfill unmet needs for characterizing heterogenous pathophysiological drivers of ADRD beyond amyloid and tau. We will focus on developing blood- based biomarkers of synaptic loss, use two new, large, deep proteomic datasets in CSF and in plasma to identify new candidate biomarkers for ADRD research, refine our multi-pathophysiology panels of CSF and plasma biomarkers to characterize the relative contributions of vascular, metabolic, inflammatory, and other processes, and work with the Neuropathology Core to develop novel seeding assays of α-synuclein and tau proteoforms for CSF. Aim 3) Train the next generation of clinical laboratory and translational investigators. We will train scientists in biomarker research for ADRD with the REC and educate professionals with the ORE and Clinical Cores in the use and interpretation of biomarkers in evaluation and management of ADRD. Aim 4) Diversify ADRD researchers, research participants and research. We will continue to enhance opportunities for trainees and junior faculty from underrepresented in medicine (UiM) groups and increase underrepresented group participation in blood and CSF research via engagement with ORE Core activities, relationship-building efforts, dissemination and a focus on biomarker tools for personalized medicine.