PROJECT SUMMARY -NEUROPATHOLOGY CORE Autopsy remains the gold standard for the diagnosis of diseases that cause dementia. It provides knowledge essential for developing biomarkers, understanding cellular pathology responsible for the dementia, and retrospectively identifying features most reliable for early diagnosis. Without this information rational discovery of disease-modifying drugs for dementia syndromes would not be possible. The Neuropathology Core will pursue the dual goals of fulfilling national priorities set by NIA and NAPA while also fostering the ‘Heterogeneity in Aging and Dementia’ theme of the Northwestern ADRC. These goals will be achieved through the following interactive aims: 1) Provide state-of-the-art postmortem diagnosis on Clinical Core participants and make the results available in a timely fashion to family, clinicians, qualified researchers, and NACC. 2) Collect, curate, and distribute biospecimens to qualified research projects, both within Northwestern University and for multi-center collaborations including NCRAD and ADGC. 3) Support the specialized research interests within Northwestern University on unusually successful cognitive aging (SuperAgers), non-amnestic dementias such as primary progressive aphasia (PPA), frontotemporal lobar degenerations (FTLD), neuroinflammation, and mid-life onset AD (MOAD). 4) Support local research on clinicopathologic correlation through a banking protocol that emphasizes bilateral tissue sampling for detection of hemispheric asymmetry and through stereology and densitometry for quantitative comparisons of cellular pathology with in vivo clinical and imaging data. 5) Train the next generation of neuropathologists in a multidisciplinary setting that includes close interaction with clinicians, imagers and neuroanatomists and in a manner that serves the goals of the Research Education Component. Integrating the cellular basis of the disease with its clinical manisfestations requires close interaction among neuropathologist, neuroanatomist, imager and clinician to link the nature and distribution of the neuropathology to the clinical phenotype and its trajectory. To this end, monthly CPC meetings provide an interactive setting for superb training of fellows in rigorous diagnosis, clinicopathologic correlation and potential collaborative research. The ADRC Brain Bank and Neuropathology and Imaging Biomarker Core laboratories, as well as Core Leader and Director offices and other resources, are located in contiguous space on the same floor. This infrastructure offers a dynamic incubator for multidisciplinary interactions between the Neuropathology Core and other components of the ADRC.