The Cellular Modeling Core for MARMO-AD

PROJECT SUMMARY CELLULAR MODELING CORE (CMC) The mission of the Cellular Modeling Core (CMC) is to support the longitudinal phenotypic characterization of in vitro marmoset models of Alzheimer’s Disease (AD). The long-term goal of the CMC is to contribute toward understanding healthy aging trajectories and identifying divergent phenotypic changes in early-onset AD (EOAD) and late-onset AD (LOAD) marmoset models developed in the MARMO-AD Research Projects. Specifically, the CMC will collaborate with the VCMC to obtain fibroblast skin biopsies and ex vivo primary astrocyte and neuronal cultures from prematurely demised animals. The CMC will also use state-of-the-art protocols to optimize human cellular reprogramming and differentiation techniques to study cellular disease mechanisms of neurons and astrocytes. Furthermore, the CMC will establish pipelines for comprehensive characterization of amyloid-β (Aβ) generation, pathological tau accumulation, neuroinflammation, and neuronal stress in both primary and differentiated cellular cultures throughout the lifespan of each animal. Finally, the CMC will work alongside the MDCC and BDIC to correlate longitudinal omics, behavioral, and biological data obtained in vivo with in vitro functional cellular assays. The primary aim of the CMC is to maximize the utilization of the marmoset AD models by generating a robust pipeline to compare in vivo with ex vivo and in vitro assessments that leverage the use of primary cells as minimally invasive surrogates of brain trajectories during the marmoset lifespan and development of AD. Work in the CMC will be invaluable in translational research to elucidate cell-specific pathogenic mechanisms and create a novel cellular resource for the AD and broad neuroscience community.