ABSTRACT The University of California San Francisco Alzheimer’s Disease Research Center (UCSF ADRC) is a major catalyst for a broad spectrum of research in Alzheimer’s Disease and Related Dementias (AD/ADRD) conducted at UCSF and has served as a cornerstone for national and international multi-site diagnostic and treatment studies. In four previous cycles of funding, we have organized a critical mass of AD/ADRD research and share our resources widely. The central theme of the ADRC is “heterogeneity in dementia,” with a focus on young- onset and atypical presentations of AD/ADRD in diverse populations. We excel in clinical phenotyping, imaging, biospecimen analysis, and pathologic characterization of large and unique cohorts of early-onset and atypical AD, frontotemporal dementia (FTD) spectrum, Traumatic Encephalopathy Syndrome (TES)/Chronic Traumatic Encephalopathy (CTE), Creutzfeldt-Jakob disease (CJD) and functionally intact controls. The ADRC supports and effectively leverages additional NIH and foundation funding, philanthropy, and industry collaborations to accomplish its aims. In the past cycle, ADRC resources were utilized by 47 R grants, 18 K awards, six U grants, two T grants, six non-federal training grants and 59 clinical and industry sponsored trials. In this P30 renewal application, we accelerate efforts to define subtypes of healthy aging, mild cognitive and behavioral impairments (MCI/MBI), AD, TES, FTD spectrum and prion diseases, improve early recognition and tracking of transitions from normal aging to dementia, and stimulate drug development and clinical trials. The ADRC will consist of seven cores: Administrative, Clinical, Data Management and Statistics (DMS), Pathology, Outreach Recruitment and Engagement (ORE), Imaging, and Biomarker and a Research Education Component (REC). These cores will work to pursue the following overarching Specific Aims: Aim 1: Explore the features of brain aging, MCI/MBI, AD, FTD-spectrum disorders, TES/CTE and CJD to better understand their clinical, genetic, pathological, and molecular underpinnings via data collected in the Clinical, Path, Biomarker, and Imaging Cores. Aim 2: Promote innovative research on early and accurate diagnosis, novel treatments, and future prevention of heterogeneous AD/ADRD by sharing data, images and biosamples from our unique clinical cohorts with local investigators, the ADRC network (via NACC, SCAN and NCRAD) and the broad research community. Aim 3: Recruit Chinese Americans, Latino Americans and Black/African Americans to the Clinical Core and offer education to these communities through the ORE Core. Aim 4: Develop innovative approaches to data management and biostatistics in the DMS Core to support easy access and analysis of ADRC-related data, while offering statistical support to our investigators. Aim 5: Train new leaders in research via the REC and educate community professionals and laypeople through the ORE Core using approaches that highlight the heterog...