ABSTRACT – OVERALL The overall goal of the proposed Rush ADRC is to create an inter-disciplinary environment that supports innovative research on the causes, treatments, and prevention of AD/ADRD. While the proposed Rush ADRC is for a new grant, it builds on three decades of work by the current Rush ADCC. The Rush ADRC has eight cores and one component, which align with the recommendations of the 2017 NIA strategic plan, including studies that: 1) recognize the heterogeneity and multifactorial nature of dementias; 2) support extensive molecular profiling to fill the gaps in large-scale human data needed to build predictive models of disease and wellness; 3) employ new research paradigms, e.g., systems biology, human cell modeling; 4) enable rapid and extensive sharing of data, disease models, specimens, and support open and team science; 5) develop computational tools and infrastructure for storage, integration, and analysis of large-scale biological and patient-relevant data; 6) build multidisciplinary translational teams in virtual and real spaces; 7) develop new pre-competitive public-private partnerships; 8) change academic, publishing, and funding incentives to promote collaborative, transparent, and reproducible research; and 9) engage patients, caregivers, and citizens as direct partners in research. The Administrative Core will provide scientific leadership to the Rush ADRC as a whole. The Religious Orders Study (ROS) Core will recruit and conduct annual evaluations of Catholic clergy without dementia who agree to organ donation. The Clinical and Latino Cores will collect data harmonized with on Blacks and Latinos without dementia and work to obtain brain autopsy. The Neuropathology Core will process, store, evaluate and distribute biospecimens obtained by the Clinical, ROS, and Latino Cores. The Outreach, Recruitment, and Engagement Core will provide a wide range of educational programs to support outreach and recruitment of racial and ethnic minorities into the Clinical, ROS and Latino Cores, and other NIA funded initiatives. The Biomarker/Neuroimaging Core will process neuroimaging generated with other funds from all three Cores and affiliated studies, and document neuroimaging and biofluid biomarker data. The new Research and Education Component will provide structured mentoring of students and faculty at all levels. The Data Management and Statistical Core will provide the infrastructure that allows all other Cores and the REC to be maximally successful and impactful and will provide statistical support to users of ADRC resources especially junior investigators and trainees.