The Boston University Alzheimer’s Disease Research Center Clinical Core (BU ADRC CC) facilitates and conducts cutting-edge research on AD and AD related dementias (ADRDs), including chronic traumatic encephalopathy (CTE). CC participants, and biospecimens and data generated from their participation, support local efforts, cross-ADRC collaborations and national research initiatives. CC investigators are engaged in AD/ADRD research towards several National Alzheimer’s Project Act (NAPA) goals, including population studies, precision medicine, health disparities, biomarkers, diagnosis, mechanisms, and translational and clinical research. The Center is closely integrated and synergistic with the Framingham Heart Study at BU. Research by CC investigators has led to fundamental insights into the role of repetitive head impacts (RHI) from contact sport participation, military service and physical violence in the pathogenesis of AD/ADRD, including CTE. However, CTE cannot be diagnosed during life due to an ill-defined clinical presentation and lack of validated biomarkers. Research has been limited by cross-sectional studies of small samples of male former elite American football players and reliance on retrospective informant reports. To address these knowledge gaps, we expanded our CC in 2018 to integrate participants with exposure to RHI (men and women, across different types of sports and levels of play). This integration is highly aligned with the Center-wide theme to study the late effects of RHI and compare AD, CTE and other ADRDs, vis-à-vis clinical presentation, biomarker profile, genetic and other risks factors, and clinical-pathological correlations. In Aim 1, we will sustain, augment, and characterize the clinical phenotypes and trajectories of an established CC Cohort (CCC). The CCC is comprised of 400 participants, that are >50 years, demographically diverse, representative of Greater Boston and that span the cognitive spectrum. We will collaborate with the Outreach, Recruitment and Engagement Core to continue recruitment of traditional CC participants and expand the number with RHI exposure. We will characterize the neurological, neuropsychological, neuropsychiatric and diagnostic profiles using traditional and novel phenotyping approaches, including digital phenotyping. We will obtain brain donation consent of CC participants and work with the Neuropathology Core to facilitate brain donation. In Aim 2, we will obtain brain imaging, biospecimens and novel biomarkers from the CCC and work with the Data Management & Statistics, Biomarker, and Genomics and Molecular Profiling Cores to integrate biomarker collection, analysis, banking, and distribution. In Aim 3, we will share data and provide a source of well-characterized participants for local and national research studies on AD and ADRD, including CTE. In Aim 4, we will educate trainees to develop the next generation of AD/ADRD clinical investigators. In conclusion, the CC plays a central ...