PROJECT SUMMARY - OVERALL The overarching goal of the renewal of the Wisconsin Alzheimer’s Disease Research Center (ADRC) is to conduct breakthrough research on the pathobiology, preclinical biomarkers, early diagnosis, treatment, and prevention of Alzheimer’s disease (AD) and related dementias. This goal will be accomplished by establishing a stimulating, interdisciplinary environment for collaborative, equitable, and generalizable research that provides invaluable clinical data, ante-mortem biospecimens, and autopsy brain tissue. Funded by NIA in 2009, the Wisconsin ADRC will oversee eight well-integrated Cores and the Research Education Component that will support timely, innovative research, which will: 1) characterize preclinical biomarkers of AD and their role in predicting transition from preclinical to clinical stages of the disease; 2) investigate the neurobiology of AD; 3) identify novel vascular and genetic risk factors, linking them to the disease pathology and clinical phenotype; 4) incorporate contemporary biochemical and molecular techniques into clinical-pathologic cohort studies, including multidimensional omics and next generation sequencing; and 5) participate and facilitate the missions of other federal, state, and local agency-supported aging and dementia research programs. The overall goals of the Center will be accomplished through coordinated activities of its eight Cores and the REC. The Administrative Core will provide scientific leadership to the ADRC. The Clinical Core will perform standardized evaluations and collect UDS and additional data on all research participants. It will work closely with the Outreach, Recruitment and Engagement (ORE) and the Inclusion of Underrepresented Groups (IURG) Cores to enhance enrollment of participants from underrepresented groups. The Data Management and Statistical (DMS) Core will continue to meet all data management, informatics, and statistical needs and support all the PC- and web-based services and processes. The Neuropathology Core will continue to provide neuropathologic diagnoses and process, store, and distribute antemortem biospecimens and postmortem brain tissue to support novel research in AD. The ORE Core will provide a broad-range of educational and community outreach programs about AD and support the Wisconsin ADRC’ goal to recruit research volunteers, especially those from URGs into the Clinical Core and other NIA-funded initiatives, such as ACTC, ADCS, ADNI, NCRAD and GWAS studies. The IURG Core will work closely with the ORE and Clinical Cores to enhance recruitment and retention of URG participants into the ADRC. The Biomarker Core will support and provide access to resources in preclinical neuroimaging and fluid biomarkers of AD. The REC will coordinate closely with the Clinical, ORE, IURG, Neuropathology, and DMS Cores to provide state-of-the-art, competency-based training to learners of varied backgrounds and levels of training, including high school students, u...