OVERALL ABSTRACT The Northwestern ADC is in its 21st year. This proposal aims to establish an Imaging Core to address an unmet need for the Northwestern Alzheimer?s Disease Center (ADC). In this ?Overall? component of the application, the specific aims, innovation and approach sections will address the impact of the revision on the entire Northwestern ADC. The section on the proposed Imaging Core will address these aspects from the focused vantage point of imaging methodology, infrastructure and scientific content. Nearly all of these Specific Aims will be enhanced by the availability of the Imaging Core. The proposed Core will extend the mission and mandate of the ADC by: ? Improving the characterization and diagnostic classification of Clinical Core subjects; ? Adding quantitative and uniformly standardized imaging-based biomarker information (e.g., atrophy, blood flow, connectivity, amyloid, tau, etc.) to the data entered into NACC modules; ? Unburdening researchers using Clinical Core subjects from the need to gather ad hoc imaging data; ? Increasing the range of hypotheses that can be addressed by collaborative projects relying on Northwestern ADC resources (e.g., collaborators can request cognitively healthy controls with or without elevated amyloid PET to address their hypotheses) Specific examples are provided in the letters of support; ? Adding a new dimension to clinicopathologic investigations of autopsy specimens (e.g., what is the relationship between atrophy measured by MR imaging and the number of neurons, microglia, neurofibrillary tangles?).