PROJECT SUMMARY – NEUROPATHOLOGY CORE The Neuropathology (NP) Core performs diagnostic evaluations, quantitative analyses on brain tissue collected at autopsy of participants in the Mayo Alzheimer Disease Research Center (ADRC), allowing feedback to clinicians, closure to family members and contribution to research by providing scientists postmortem brain samples and data derived from those samples. The NP Core provides support to ADRC-affiliated investigators and to outside investigators. The neuropathologic and genetic data are communicated to the Data Management and Statistical Core, who uploads it to the National Alzheimer Coordinating Center (NACC). The research approach for the NP Core is as follows: Specific Aim 1. Perform brain autopsies on a diverse population of participants of the Mayo ADRC in a timely fashion and according to protocol, which includes collection of fixed and frozen tissue, postmortem CSF and demographic and clinical data related to these samples. Specific Aim 2. Provide neuropathologic evaluations and collect neuropathologic data using standardized methods for gross dissection and neurohistology. Assign AD likelihood diagnoses based upon Thal amyloid phase, Braak NFT stage, and CERAD neuritic plaque score using the NIA-AA ABC diagnostic probability scheme. Arrive at a consensus on clinicopathologic diagnoses and educational opportunities at videoconferences. Record neuropathologic data with NACC Version 11 and provide data to the Data Management and Statistical Core and NACC. Specific Aim 3. Generate quantitative endophenotypes using digital pathology and image analysis in support of ADRC research. Specific Aim 4. Store brain fixed and frozen tissue and other autopsy-derived materials and provide clinically and pathologically well-characterized tissue samples to investigators at Mayo Clinic and outside institutions supporting biochemical and biomarker discovery. Frozen tissue is continuously monitored by an electronic system and available backup freezers to ensure high-quality sample preservation.