BIOSPECIMEN CORE: PROJECT SUMMARY/ABSTRACT The overarching goal of our “3-D Aging & Alzheimer Brain Program” is to define, using single cell-based approaches with spatially-resolved transcriptomic and proteomic measurements, the effect of aging and Alzheimer’s disease (AD)-related pathologies on the brain in three dimensions and the relation of these effects on cognitive decline. Crucial to achieving this goal is consistent access to well-phenotyped, high quality, human brain tissue that has been consented for broad data sharing. The Biospecimen (BIO) Core will be responsible for compiling one of the largest collections of tissue across the lifespan and known pathological hallmarks of AD by continuing prospective collection of comparably phenotyped high quality cases at the University of Edinburgh, the Rush Alzheimer’s Disease Center, and the New York Brain Bank (NYBB). The goal of the BIO Core is to link clinical-pathologic data with contemporary molecular techniques from brain tissue to facilitate innovative research studies on aging and AD. The BIO core will (1) support each of the four Projects by identifying, preparing, and distributing the best available samples for each aim, (2) determine the plane of section for each sample, and (3) assemble standardized outcome measures from each sample. The BIO Core will also support the innovative methodological development of the Spatial Multiomics (SM) Core through the acquisition and provision of high-quality molecular grade tissues. In parallel, the harmonized phenotypic data will flow to the Integrated Computational Analysis (ICA) Core which will align the phenotypes with data for each of the Projects. A Laboratory Information Management System (LIMS), managed by the Administrative Core, will be used to organize and track all sample characteristics, enabling a structured evaluation of the sample selection and preparation process to uncover any areas of weakness and identify new quality measures. In summary, the BIO Core will significantly enhance the quality, annotation, and re-purposability of the data produced by this Program and its processes and protocols will help guide and enhance improvements in tissue processing for the wider neurodegenerative disease community.