ABSTRACT Clinical neuroimaging of Alzheimer’s Disease (AD) subjects is a critical aspect of understanding disease onset, progression, and response to therapies. The UCI MODEL-AD team is developing new mouse models of AD that more readily recapitulate the human disease. As new mouse models are generated by the Disease Model Development and Phenotyping Project (DMP), the Neuroimaging and Neurovascular Core (NIVC) will undertake a compendium of imaging modalities to deeply phenotype these mice using clinically relevant, magnetic resonance imaging (MRI) sequences to probe structure, tissue cellularity, and physiological functions in an age, sex and diet dependent manner. The NIVC will also undertake a novel vessel-painting approach that labels the cerebrovasculature. The goals of the NIVC are to significantly increase our structural and functional understanding of how the MODEL AD mouse brain responds to genetic perturbations reminiscent of human AD and to link these discoveries to clinical AD imaging. To accomplish these goals, we will undertake four Aims. Aim 1 is to determine deep MRI and vascular phenotypes for DMP base-platform mice and high-interest models. This Aim will use standardized (Alzheimer’s Disease Neuroimaging Initiative; ADNI-derived) and innovative multimodal MRI techniques to describe structural, vascular, structural/functional connectivity, and metabolic signatures in emerging AD mouse models. Aim 2 is to facilitate biomarker development by integrating MRI with histopathological and multi-omic data. Here, NIVC data will be merged with DMP and Functional Genomics Bioinformatics Data Management Core (FGBDMC) data to identify biomarker signatures on neuroimaging data that provides insights on the underlying AD neurobiology. Aim 3 will validate potential MRI biomarkers emerging from recent human AD studies, which include spectroscopic imaging and quantitative susceptibility mapping. Aim 4 is to disseminate MODEL-AD neuroimaging and vascular findings to the larger international AD community and to provide entry to new researchers interested in AD. In summary, the NIVC will: 1) innovate new imaging approaches for phenotyping mouse models and make these data publicly available for AD researchers, 2) collaborate with human and mouse neuroimaging groups to pursue evaluation of potential predictive markers that could guide early clinical diagnosis of AD, 3) educate the scientific (students, postdocs, new researchers) and the broader public community about AD, and, 4) translate the NIVC findings to provide new directions for neuroimaging approaches to aid diagnosis and monitor treatment response of human AD.