Project Summary/Abstract: Neuropathology Core? The Neuropathology Core is aligned to support the overall specific aims of the OADC's 5 overarching aims: 1) catalyze and sustain innovative research and discovery in AD and related disorders through an organizational infrastructure supporting a rich collaborative environment; 2) focus resources toward specific areas of emphasis: preclinical dementia and activity of disease emphasizing the oldest old; markers of meaningful change captured through studies of peripheral biomarkers, neuroimaging and continuous in-home behavioral monitoring; neuropathology of brain aging and late life dementia; novel testing of novel treatments; and improving education and knowledge about dementia; 3) provide materials to support the science through well- characterized research participants, biological specimens, brain tissue, data provision and analytics; 4) contribute to the national research commons relevant to AD and related disorders; and 5) provide venues and mechanisms for education and training of new scientists, as well as educating and informing key stakeholders. The focus of the OADC's Neuropathology Core on the transition from healthy aging to dementia has led to the accumulation of a large repository of tissue from cognitively intact brain donors and from those who develop dementia and milder impairments at a more advanced age, with pathologies that differ somewhat from those of classic Alzheimer's disease. Understanding these changes in the context of the clinical and imaging findings in these individuals is proposed as the scientific leitmotif around which the Specific Aims are constructed. These are to: 1. Provide standardized research assessments while at the same time affording this diagnostic expertise to the population of OADC subjects by providing family members of the deceased and physicians involved in their care with timely autopsy reports based on the most current standardized diagnostic criteria. 2. Facilitate research by collecting, storing and distributing a highly accessible, but appropriately safeguarded, repository of well-prepared brain tissue and neuropathologic data from carefully and longitudinally characterized patients with mild cognitive impairment (MCI) or dementia as well as non- cognitively impaired individuals using a variety of methods that maximizes utility to scientists. 3. Teach trainees in pathology, neurology, psychology, psychiatry, and basic sciences the current methods of neuropathological classification of neurodegenerative diseases and age-related changes, and mentor faculty in NP. 4. Develop innovative new approaches to maximize achievements in Aims 1 to 3.