Project Summary/Abstract: Clinical Core The Clinical Core of the UK-ADC maintains a well-characterized, community-based cohort focused on normal aging and early transitional disease states, and follows individuals longitudinally until brain autopsy. We maintain a mandatory autopsy requirement for all subjects (with the exception of our Minority Gateway Clinic, where autopsy is promoted but not required), allowing major contributions in the area of clinical- pathological correlative studies, definition of early preclinical and pre-dementia disease state pathology, and basic translational research. The UK-ADC Clinical Core emphasizes: 1) collection of demographic, clinical, genetic, and autopsy data from large numbers of subjects, readily available as potential research subjects for current and future research needs, 2) provision of non-autopsy biospecimens including antemortem imaging and CSF biomarkers in a sub-cohort of subjects, and 3) efforts to further advance the discovery and development of novel therapeutics for AD. We are major contributors to national collaborative initiatives such as NACC, ADCS, ADNI, NCRAD, and ADGC. Our research cohort is strongly motivated to participate in research, as evidenced by 304 unique, active (living) subjects who have participated in clinical studies over the report period. The Clinical Core has supported 40 grants and affiliated projects focused on specific research questions beyond standard UK-ADC data collections, culminating in 64 direct and 18 indirect publications supported by Core activities. Antemortem biomarker collections over the current funding cycle include 361 clinical and 267 standardized research MRI scans, 229 CSF collections, and 90 A?-PET scans in order to more fully characterize our normal control and early transitional (MCI) cohort. Another major strength of our center lies in our robust minority outreach and engagement. Our efforts, in conjunction with the OR Core, have led to above-par, for local and regional area, minority engagement in ADC and affiliated studies. We have effectively engaged minority subjects in perceived invasive and therapeutic research efforts at a level of participation that has previously been considered untenable by most ADCs and non-NIA funded centers nationally (37.6% unique minority subjects engaged in interventional trials). These efforts and successes will continue in the next five years under the harmonized and integrated Clinical Core efforts that have proven successful at the UK-ADC. We will continue to play a leading role in clinical translational research and development of potential novel therapeutic strategies to prevent or modify pathogenesis of AD and related disorders. Overall, the Clinical Core will continue to provide an infrastructure and environment that will continue to contribute to our success in advancing multidisciplinary, innovative AD research supporting our center theme of Transitions & Translation.