CORE D: NEUROPATHOLOGY - ABSTRACT The UCSD-ADRC Neuropathology Core has been instrumental in providing support for establishing the accuracy of clinical diagnosis of Alzheimer's Disease (AD) and dementia with Lewy bodies (DLB), delineating structural and clinico-pathological correlates of dementia in AD, identifying new neuropathological entities causing dementia, provide tissues to investigators and helping to better understand the mechanisms of synaptic degeneration in AD. For the renewal the Aims of the Neuropathology Core will be to: 1) perform rapid autopsies and procure brains from the ADRC participants, using a standardized protocol; 2) perform standardized neuropathological diagnoses and immunocytochemical analysis of demented and normal aged (control) patients clinically evaluated by the UCSD ADRC following the new NIA criteria; 3) maintain a state of the art brain repository to provide the ADRC projects and other investigators with well characterized including early AD and MCI cases; 4) perform immunochemical analysis relevant to neurodegeneration and synapse loss in MCI and early AD cases and 5) foster the utilization of the ADRC Neuropathology tissue repository for new research and inter- center collaborations. Approximately 50 to 60 cases and over 20 tissue requests will be processed a year. The neuropathological results will be submitted to the National Alzheimer's Coordinating Committee (NACC) in compliance with NIA requirements. As part of the mission of the Core we will also continue to support extensive collaborations with national and international investigators and train fellows, residents, graduate and undergraduate students in neuropathology and microscopy techniques. Support ADRC Projects including providing post-mortem confirmation and analysis of SORL-1 for Project 1, FTD tissues and analysis of C9ORF for Project 2, and providing brain tissues from control, MCI, AD for Project 3. With the ADRC Outreach, Recruitment and Education (ORE) Core organize meetings to encourage the use of the neuropathology core. New and junior investigators will be encouraged to conduct research with the postmortem tissues. Continue to provide tissues to local and national investigators and for multi-center initiatives such as the Genome-Wide Analysis Studies organized by NIA.