Understanding the complexity of heterogeneous and intersecting neurodegenerative disorders entails comprehensive qualitative and quantitative assessment of the central nervous system. Hence, the Neuropathology Core (NPC) is a pivotal component of the South Texas Alzheimer Center (STAC). Co-led by Kevin Bieniek, PhD and Jamie Walker, MD PhD, both trained especially for establishing and leading a new Brain Bank, this core comprehensively characterizes brain and spinal cord confirming clinical diagnoses, for purposes of research, and to provide a diagnosis and advice to families. Future advancements in elucidating and intervening in the pathogenesis of Alzheimer’s disease and related dementias (ADRD) requires the study of diverse ethnoracial autopsy cohorts. The STAC NPC services a large Mexican-American Hispanic population in the South Texas region. It will generate normative (cognitively normal) and preclinical, clinical ADRD (AD, FTD/ALS, DLB, PSP, CBD, VCID) data on MA Hispanic persons. Although our current brain samples are only 15% Hispanic, our fluid biobank has over 70% Hispanics and our focused attention on recruitment should increase the proportion of Hispanic brains to over 50% over the next 5 years. A 24/7 no-cost, autopsy service, post-mortem MRI, ante-mortem imaging/clinical assessments, family interviews, medical records increase the value of tissue obtained and shared with NACC. Interpreting ethnoracial pathological heterogeneity necessitates consideration of genetic and molecular variation, hence STAC has undertaken routine WES on the 56 brains donated to date (a 400% increase since our original submission) and proposes to undertake clinical genetic testing (with genetic counseling) in families of registered donors (Clinical and Genetics/Multiomics Cores), WGS on donated brain tissue and routinely preserves frozen brain tissue for additional omic (methylation, transcriptomics, ATAC-Seq, proteomics, metabolomics) studies. The NPC employs state-of-the-art genetic and “omics” approaches to aid in the interpretation of ADRD pathologies and identification of novel disease modifiers. The NPC undertakes routine digital scanning of all slides, and spatial neuropathology. The aims of the NPC are: accessioning high-quality central nervous system autopsy biospecimens, including brain, spinal cord, skin and cerebrospinal fluid (Aim 1); conducting data driven neuropathological evaluations of this material (Aim 2); maintaining these resources in a dynamic biorepository for use by a range of investigators (Aim 3); leading translational neuropathology research of multi-etiology dementia, including those of degenerative, cerebrovascular, and traumatic origins (Aim 4); and educating the local scientific/trainee (REC) and lay public communities on the importance of neuropathology and neurodegeneration research (Aim 5). The Neuropathology Core will accomplish these aims through collaborative relationships with other STAC Cores and external investigators, including colleagues at other Alzheimer’s Disease Centers.