PROJECT SUMMARY The goals of the Neuropathology Core (NPC) are to perform standardized postmortem neuropathological evaluation, and classification of subjects recruited by the Cleveland Alzheimer's Disease Center (CADRC), and to collect, store, and analyze fixed and frozen autopsy materials for use in future research. Drs. Cohen and Appleby, who bring expertise in the areas of molecular pathology and clinicopathologic correlation of neurodegenerative disease, will lead the NPC. To support AD research projects, the NPC will perform all tissue processing for histology and freezing, and immunohistochemical investigations of Alzheimer's disease (AD) and related dementias (ADRD). The NPC will also characterize archival tissue of AD cases in the brain banks at participating sites, to more rapidly make available tissues for investigation. The goal of the CADRC NPC is to obtain, characterize, and maintain neuropathologic specimens from subjects affected by AD and related dementias (ADRD). With over two decades of experience in conducting autopsies from across the country and maintaining neuropathologic tissue, the CADRC NPC will be maintained via infrastructure that has been proven through the work of the National Prion Disease Pathology Surveillance Center (NPSPSC) (Specific Aim 1). Experts in the field of neurodegeneration (Drs. Cohen and Leverenz) will characterize neuropathologic specimens according to accepted standardized criteria (Specific Aim 2). The CADRC will have access to and will help characterize a unique cohort of ADRD samples obtained through the NPDPSC (Specific Aim 3). Finally, the NPC will foster the next generation of AD researchers by training and mentoring junior faculty in neuropathology and current concepts of basic neuroscience of age-related neurodegenerative diseases (Specific Aim 4). We anticipate the CADRC NPC to provide essential infrastructure to greatly facilitate and integrate independent research on ADRD that are currently active at a local, national, and international level.