Overall ? Project Summary This application proposes a new Alzheimer's Disease Core Center (ADCC) at Wake Forest School of Medicine (WFSOM) to provide a comprehensive infrastructure for research on the pathophysiology, prevention, and treatment of AD. Our Center will provide innovative resources to examine the contributions of metabolic and vascular factors to early phase transitions from normal aging to MCI and then to AD and other dementias, through coordinated research spanning the translational spectrum. Wake Forest is uniquely equipped to rapidly develop a high-impact ADCC because it has: 1) a deep, interdisciplinary foundation in aging research; 2) specialized expertise in metabolic and vascular factors and their relationship to cognitive aging and dementia; 3) strong ties to an ethnically diverse community with high prevalence of dementia and metabolic/vascular disorders; and 4) exceptional institutional support. The rationale for our theme is based on research showing that metabolic and vascular disorders are highly prevalent, modifiable factors that contribute to the transitions from normal aging to MCI, AD, and other dementias. To promote innovative translational research focused on these factors, the ADCC will enroll an observational multi-ethnic cohort from an existing 15-year study of metabolic/vascular risk, and leverage their extensive data by adding key endpoints to characterize AD and other dementias. The Clinical Core will enroll a separate cohort enriched for metabolic/vascular risk, along with participants with AD. The ADCC will focus on African-American (AA) and other underserved groups who are twice as likely to develop AD, and have high rates of diabetes and vascular disease. Specialized resources will be available to ADCC investigators, including non-human primate (NHP) models for translational research. A repository of human and NHP biospecimens, genetic/epigenetic data, and extensive clinical data will be available to NACC, NCRAD, and other investigators. The ADCC will also serve as a resource for a broad spectrum of AD initiatives. Our Specific Aims are to: 1) Establish a comprehensive integrated research infrastructure focused on phase transitions from normal aging to MCI, AD, and other dementias, and provide special resources to accelerate research on metabolic and vascular factors; 2) Optimize the participation of AA adults to better understand the causes underlying their increased risk of AD and dementia; 3) Expand relationships with the national ADCC network and key affiliates such as NACC and NCRAD; 4) Provide training in translational research to new investigators, and education regarding AD and dementia to professionals, patients and families, and the community. The prevalence of metabolic and vascular risk factors, their importance to AD expression, the strengths of the Wake Forest scientific community in these research areas, and our outstanding institutional commitment are indicators that NIH funding will be successfully leveraged to establish an ADCC that will make high-impact contributions to the field.