PROJECT SUMMARY—BIOSPECIMENS CORE (Core G) Fluid biomarkers hold great promise for improving early and accurate diagnosis, symptom monitoring, prognostication, and measuring treatment effects for frontotemporal dementia (FTD). Over the past 19 years, the UCSF PPG Biospecimens sub-core (as part of the Neuropathology Core) has successfully collected, banked, and shared human biofluid specimens from over 2,000 research participants. In parallel, we have leveraged the strength of the UCSF neurodegenerative disease research community and multiple public-private collaborations to build infrastructure in fibroblast banking to enable induced pluripotent stem cell (iPSC) preparation. This newly proposed Biospecimens Core will synergize these resources to support this PPG's mission of improving the early and accurate diagnosis and tracking the progression of FTD. The Biospecimens Core will be led by Dr. Adam Boxer, a leader in neurodegenerative fluid biomarker development. He also co-directs the ALLFTD Consortium (U19AG063911) including its Biofluids Core. Serving as Co-Leader will be Dr. Aimee Kao, a neurologist- physician-scientist whose research focuses on the basic pathophysiological mechanisms underlying FTD, Alzheimer's Disease, and related disorders. She brings experience and expertise in fibroblast and iPSC culture and banking, and she serves as Lead of the UCSF ADRC Biomarker Core. We propose three aims. In Aim 1, this Biospecimens Core will work with the Data Management and Biostatistics Core to support the Clinical Core with blood, CSF, and epithelial fibroblast collection from research participants. In Aim 2, the Biospecimens Core will provide measures of established fluid biomarkers such as plasma and/or CSF Aβ1-42, Aβ1-40, total tau, P- tau217, and neurofilament light chain (NfL) as a basis for Amyloid [A], Tau [T], Neurodegeneration [N] classification of all participants. Aim 3 will support the PPG projects and work towards discovery and validation of novel biomarkers through establishment of proteomic and lipidomic datasets and collection of FTD epithelial fibroblasts, thus enabling iPSC line generation. Information will be iteratively shared with the Neuropathology Core to drive scientific insights into disease pathophysiology. This Biospecimens Core will also collaborate with the Imaging Core on development of novel neuroimaging measures in conjunction with validation of new plasma diagnostic biomarkers. By leveraging established agreements with the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD), this Biospecimens Core will continue to bank and share a large longitudinal collection of exquisitely well-characterized patient and control biospecimens, positioning this core to support research projects locally, nationally, and internationally.