Imaging Biomarker Core – Project Summary The Imaging Biomarker Core (IBC) of the Alzheimer’s Disease Research Center (ADRC) at Wake Forest School of Medicine will address a critical need to establish biomarkers that reliably differentiate Alzheimer’s disease (AD) from other conditions that affect cognition in aging. Recently, an AD research framework was developed for a biologically-based classification to enhance identification of disease mechanisms, to appropriately target therapeutic interventions, and to track therapeutic response and disease progression. Neuroimaging techniques, such as magnetic resonance imaging (MRI) to measure structural changes and positron emission tomography (PET) to track changes in pathological hallmarks such as beta-amyloid and tau, comprise a powerful approach to characterize the progressive pathology associated with cognitive decline and to differentiate AD from other dementias. To establish reliable biomarkers associated with AD and other conditions that impair cognition with aging will require a large collaborative effort and the national ADRC network is ideally suited to address this need. The Wake Forest ADRC can make unique contributions to the network. The IBC will conduct longitudinal, multimodal neuroimaging paired with phenotypic and genomic characterization of a diverse cohort of participants. The IBC will provide expertise and resources to complement the ADRC’s themes that focus on: 1) early transitions from normal aging to mild cognitive impairment (MCI) and AD; 2) the role of metabolic and vascular risk in these transitions; and 3) the nature of these relationships in persons from underrepresented groups (URGs). The first aim of the IBC will be to leverage the Clinical Core and extensive existing Wake Forest imaging infrastructure, including research- dedicated PET and MRI, cyclotron, and advanced analytic pipelines, to conduct state-of-the-art longitudinal imaging to help identify the causes of AD and develop novel strategies for prevention and treatment. As a second aim, the IBC will integrate imaging data with clinical, biomarker, and other research data to facilitate scientific discovery. The third aim will be to develop imaging methods for animal models of AD, and the final aim will be to provide training and consultation on the latest scientific advances in neuroimaging to ADRC- affiliated investigators and trainees. Through these aims, the Wake Forest ADRC IBC will further the understanding of AD pathology and its relationship to cognitive decline and will significantly enhance the Center’s contribution to the ADRC network and to investigators worldwide.