PROJECT DESCRIPTION/ABSTRACT – 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), and genetic testing of known and novel genetic variants. The NP Core provides support to ADRC-affiliated investigators and to outside investigators. The neuropathologic and genetic data generated by the NP Core is communicated to the Data Management and Statistical Core, who uploads it to the National Alzheimer Coordinating Center. The research approach for the NP Core is as follows: Specific Aim 1. Perform brain autopsies on participants of the Mayo ADRC in a timely fashion and according to protocol, which includes collection of fixed and frozen tissue. 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 diagnostic probability scheme. Arrive at a consensus on clinicopathologic diagnoses at videoconferences. Record neuropathologic data on NACC Version 10 and provide 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 tissue and other autopsy-derived materials and provide clinically and pathologically well-characterized tissue samples to investigators at Mayo Clinic and outside institutions. Assure security of biologic samples by using continuous electronic monitoring of freezers and by maintaining at all times at least one empty back-up freezer. Specific Aim 5. Provide genetic expertise to ADRC, as well as screening for known and newly discovered genes or common genetic risk variants for AD, Lewy body disorders (LBD) and frontotemporal lobar degenerations (FTLD).