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 therefore plays a pivotal role in all functions of the Northwestern ADC. In the next cycle, the Neuropathology Core will provide state-of-the-art postmortem diagnosis on all Clinical Core subjects that come to autopsy. The results will be made available in a timely fashion to family, clinicians, researchers, and NACC. Another key function of the Neuropathology Core will be to collect, curate, and distribute biospecimens to qualified research projects, both within Northwestern University and for multi-center collaborations including NCRAD and ADGC. In addition to supporting research related to the aging-MCI-AD continuum, the Neuropathology Core will have a special focus on unusually successful cognitive aging (SuperAgers), non-amnestic dementias such as primary progressive aphasia (PPA), and non-AD pathologies related to frontotemporal lobar degeneration (FTLD). Pursuing these themes, which constitute areas of special emphasis for the Northwestern ADC, will require bilateral tissue sampling for detection of hemispheric asymmetry and unbiased stereology for quantitative comparisons of cellular pathology with in vivo clinical and imaging data. The infrastructure of the Northwestern ADC will also enable the Neuropathology Core to train the next generation of neuropathologists in a multidisciplinary setting that includes close interaction with clinicians, imagers and neuroanatomists.