PROJECT SUMMARY Diagnostic, prognostic, and translational biomarkers are urgently needed for Alzheimer’s Disease (AD) and Related Dementias (ADRDs). The goal of this Biomarker Core is to maintain a world-class biorepository to support biomarker discovery in comprehensively characterized AD/ADRD research participants. In the last grant cycle, this Biomarker Core successfully collected, banked, genotyped, analyzed and disseminated >4,000 human biospecimens. This Core has contributed more samples to the National Cell Repository for Alzheimer’s Disease (NCRAD) than any other ADRC. As a direct result of these fluid and cell specimens, researchers at UCSF and beyond have made major contributions to neurodegenerative disease research, including validation of novel fluid-based biomarkers and new biological and genetic discoveries in AD/ADRD. Moreover, the Core’s unique Fibroblast Bank, now numbering over 300 lines, provides opportunities for generation of iPSCs and patient-derived neurons, which are becoming progressively more valuable as the field moves towards precision medicine approaches. In this renewal, the Biomarker Core will continue its long-standing contributions to the field by focusing on four critical missions: 1) collection of fluid and cell resources for biomarker discovery, 2) ensuring standardized biomarker characterization of a diverse cohort of ADRC participants enrolled by the Clinical Core, 3) expanding the toolbox of novel biomarkers, and 4) enhancing the pipeline of scientists pursuing biomarker research. Along with an anticipated ~130 annual blood samples and associated biofluids, the Core anticipates banking ~70 CSF and ~24 fibroblast samples per year. Plasma and CSF for all ADRC participants, which include a diverse representation of patients diagnosed with atypical and early-onset dementia and from historically underrepresented populations, will be characterized using the AT(N) system for biomarker-based classification of amyloid accumulation (“A” via A40, A42), tau pathology (“T” via P-tau181) and neurodegeneration (“N” via NfL), through the NCRAD project Alzheimer’s Disease Center Fluid Biomarkers. NCRAD will also provide genome-wide SNP and APOE genotyping for all participants, complemented by whole exome screening by the Core for established genetic causes of AD/ADRD. Biomarker characterization will be augmented by measures of plasma and CSF proteins reflecting synaptic and lysosomal functioning, presence of alpha-synuclein, and glial functioning with collaborator and field leader, Dr. Henrik Zetterberg. All Core activities position the team to support professional development in biomarker research for Center trainees. This work leverages a multidisciplinary team: Core Lead and neurogeneticist, Jennifer Yokoyama, PhD; Co-Leads, clinical trialist Julio Rojas-Martinez, MD, PhD and neuropsychologist Kaitlin Casaletto, PhD; and Project Manager, neuroscientist Argentina Lario Lago, PhD, all of whom have contributed to biomarke...