PROJECT SUMMARY/ABSTRACT – OVERALL (Adapted from Abstract of parent grant, UK-ADC) This is a proposal for a University of Kentucky Alzheimer’s Disease Research Center (UK-ADRC) neuroimaging supplement. This purpose of the supplement is to provide neuroimaging data on the UK-ADRC’s deeply phenotyped clinical cohort to the NIH’s recently funded initiative, Standardized Centralized Alzheimer's and Related Dementias Neuroimaging (SCAN). In addition, a secondary purpose of this supplement is to identify neuroimaging correlates of two AD-mimics: limbic-predominant age-related TDP-43 encephalopathy (LATE) and primary age-related tauopathy (PART). The UK-ADRC is an experienced and collaborative ADRC originally funded in 1985. Our principal mission is to serve as the focal point for all AD-related activities at UK and this region of the United States, by providing an environment and core resources that catalyze innovative research, outreach, education, and clinical programs. Our signature resources include: 1) a cognitively normal group of ~500 subjects followed longitudinally, with all committed to brain autopsy upon death; 2) a strong program in clinical-neuropathological correlations and short postmortem interval autopsies; 3) an established program studying preclinical biomarkers of AD using neuroimaging and biofluids; 4) an integrated centralized database and innovative biostatistical expertise to characterize clinical and biological transitions; and 5) a successful and close partnership with the African-American community and increased participation of underrepresented individuals in our longitudinal cohort and ADRC-affiliated research studies and clinical trials. The overall scientific emphasis of the UK-ADRC continues to be on our interrelated themes: Transitions & Translation. Our well-characterized, longitudinal cohort and historically strong neuropathology program focused on normal aging, preclinical disease states and early cognitive transitions have been central to our success in defining early pathogenic mechanisms underlying the transitions from normal cognitive aging to impairment. The depth of expertise and collaborative nature of our investigators have also resulted in substantial progress on translation of that knowledge into new targets and novel therapeutic strategies. The UK-ADRC provides an infrastructure and environment that focuses on these integrated themes and advances AD research, education, outreach, and clinical programs through highly interactive and effective components: Administrative Core, Clinical Core, Data Management and Statistics Core, Neuropathology Core, Outreach and Recruitment Core, Biomarker Core, and Research Education Component. The UK-ADRC will make resources from these Cores available to support the success of this ADRC neuroimaging supplement.