PROJECT SUMMARY – NEUROPATHOLOGY CORE (CORE D) The Neuropathology Core of the Wisconsin ADRC provides neuropathology expertise and infrastructure to perform rapid brain autopsies, collect and share postmortem data and biospecimens, and conduct detailed neuropathologic examination and diagnosis of brains donated to the Wisconsin Brain Donor Program (WBDP; housed in Core D) from consenting Clinical Core participants. Neuropathologic examination is performed by Board-Certified neuropathologists following NACC protocols for postmortem tissue and biofluids collection, banking, and neuropathologic evaluation, which includes state-of-the-art whole slide imaging. Critically, this in- depth neuropathologic characterization provides pathological basis for ADRC investigators to understand the role of AD and mixed-brain pathologies in AD and ADRD that contribute to clinical symptoms. The Core also supports advanced postmortem case workup for individuals with antemortem biomarkers, including postmortem MRI, image-guided tissue sampling, and collection and assessment of arterial vessels. This extensive neuropathologic characterization in conjunction with deeply phenotyped antemortem clinical, biomarker, behavioral, and genetic data collected during life uniquely facilitates cutting-edge clinicopathologic research characterizing antemortem imaging and fluid biomarkers and bridging the gap between brain pathology, ADRD biomarkers, and their clinical consequences. The WBDP works closely with Cores C, F, and G to educate participants on the impact of brain donation and encourage enrollment, and regularly communicates brain donation procedures with participants, their families, a network of pathologists, and funerary providers to ensure a short postmortem interval. Finally, the Core and its investigators collaborate with the REC to provide an array of neuropathology training resources including clinicopathologic case conferences, in-person training on gross and microscopic brain examination, and pathology coursework. The Core goals are accomplished in four specific aims. Aim 1 will perform rapid brain autopsies, collecting and archiving frozen and fixed tissue blocks from multiple brain regions on deceased individuals enrolled in the Wisconsin ADRC and linked studies, and receive, catalogue, and process relevant postmortem blood and CSF biospecimens. Aim 2 provides comprehensive neuropathologic evaluations per NIA consensus guidelines on Clinical Core subjects, collect NACC neuropathology data, and make the results available to the family, relevant clinicians, qualified researchers, and NACC. Aim 3 focuses on sharing postmortem biospecimens (brain regions, blood products, CSF) and associated neuropathologic and other data to support UW-Madison investigators, and national, and international multi-center AD/ADRD research collaborations. Finally, Aim 4 will enable innovative antemortem-postmortem research with deeply phenotyped antemortem biomarker, clinical, cognitiv...