The focus of this Neuropathology (NP) Core renewal is to collaborate with other Center Cores to achieve specific aims related to ADRD nervous system tissue acquisition, pathologic diagnosis, and research utilization and distribution. Our Core endeavors to advance understanding of neurodegenerative disease mechanisms by utilizing innovative approaches including multi-omic studies, collaborating with other Cores, and emphasizing study of diverse populations. The first aim of the NP Core is to perform tissue autopsy on diverse populations and disease states, with a continued focus on increasing the diversity of the patient cohort who receives detailed neuropathologic evaluations, particularly Latino participants. We will also prioritize collection of healthy control cases and cases with early-stage pathology. We have prioritized both of these populations at our Center and continue to increase the proportion of autopsies from these groups. Second, we will perform comprehensive neuropathological analysis and diagnosis according to the National Alzheimer’s Coordinating Center (NACC) NP Form 11 Guidelines using detailed H&E and immunostaining analysis (tau, Abeta, alpha-synuclein, and TDP-43) with data uploaded to the NACC database for sharing. Third, the NP Core will continue its onsite and collaborative research efforts to understand the mechanisms underlying neuropathologic heterogeneity and the co-occurrence of multiple pathologies. This will involve distributing banked tissue to researchers outside of our Center and, within our Center, leveraging the synergy between robust clinical neuropsychological studies, expertise in digital pathology, and ongoing collaborations utilizing RT-QuIC. Fourth, the NP Core places a strong emphasis on mentoring the next generation of NP researchers, particularly young and underrepresented scientists. We will provide resources and training opportunities, including access to ADRC tissue and core resources, to support their research and development, in collaboration with our REC core. Finally, the NP Core aims to advance novel molecular approaches using postmortem tissue, specifically focusing on cell type-specific multi-omics transcriptomics. We will integrate post-mortem transcriptomic data with data from neuronal models developed by their iPSC Core, including direct-induced neurons and iPSC-neurons. In summary, the NP Core's specific aims focus on performing tissue autopsies, executing comprehensive neuropathological analysis, managing and sharing specimen resources, mentoring young researchers, and advancing novel molecular approaches. These objectives collectively contribute to the Core's mission of advancing the understanding of neurodegenerative diseases and fostering the development of future neuropathologists and neuroscientists.