Project Summary – Neuroimaging Core (NIC) The NIC of the IADRC will serve as a regional and national resource for the aging and neurodegeneration research community by providing access to, and collaborative support for, the application of advanced neuroimaging in clinical and translational research. The NIC has been productive in developing and implementing cutting-edge protocols and techniques in neuroimaging and imaging genetics analysis, collaborating with NIA-funded initiatives (e.g., ADNI, DIAN, ADGC, etc.), and in providing training in neuroimaging and imaging genetics to scientists of all levels and disciplines. In this application, the NIC will pursue the following specific aims: (1) Support funded research in the IADRC, IU Center for Aging Research, and related programs that currently employ or could benefit from advanced neuroimaging; (2) Provide standardized, state-of-the-art neuroimaging acquisition and analysis protocols; (3) Expand transdisciplinary regional neuroscience research using advanced neuroimaging tools to study disease mechanisms and treatments for neurodegeneration; (4) Support and collaborate with major national and international AD-related research consortia using neuroimaging and genetics methods; (5) Provide transdisciplinary educational opportunities in neuroimaging and genetics of AD and other degenerative disorders for basic and clinical scientists at all levels from undergraduates to post-doctoral fellows and faculty, as well as dissemination of neuroimaging results to the community. The NIC, working closely with the Clinical Core, will perform state-of- the-art multimodal MRI (Siemens Prisma 3T: high resolution structural, 3D pCASL perfusion, multiband resting- state and task-based fMRI, and hybrid diffusion and DTI optimized for structural and functional connectome analysis) on all eligible IADRC participants, as well as amyloid and/or tau PET on >200 IADRC participants. Participants in preclinical or early symptomatic phases (e.g., subjective cognitive decline or mild cognitive impairment), late-onset AD, and individuals from families with mutations causal for dementias will be prioritized. Imaging-pathologic correlation when available will improve the understanding of early structural, functional, and molecular changes observed in vivo and may help identify novel therapeutic targets. Cross- modality image analyses and results of imaging genetics studies with ADNI, DIAN, and others will contribute to advances in early detection, mechanistic understanding, and optimize imaging as a dynamic biomarker to study therapeutic effects. Acquiring standardized state-of-the-art MRI and PET data for use by many investigators will increase research productivity and facilitate quantitative analyses. Integration with other cores will allow the IADRC to expand on these analyses by relating imaging biomarkers to neuropsychological measures, neuropathologic samples, genetic and other –omics markers. The NIC will continue to fos...