The strategic goal of the Indiana University School of Medicine Alzheimer’s Disease Drug Discovery (ADDD) Center is to integrate sophisticated capability for early drug discovery and contribute to a broader study of emerging Alzheimer’s disease (AD) target hypotheses (beyond Ab) with the goal of generating new classes of potential therapeutics. Specifically, the ADDD CENTER will establish itself as a strategic and operational partner for the NIA AMP-AD and MODEL-AD initiatives. By design, this will provide drug discovery capability to bridge the foundational work in target discovery (AMP-AD) with newly discovered lead molecules characterized in AD animal models based on human pathology, genetics and translational biomarkers (MODEL-AD). To accomplish the mission of the ADDD CENTER, we have assembled a world-class team of scientists and capabilities from Indiana University, Purdue University, and the Indiana Clinical and Translational Sciences Institute (CTSI). This team has considerable expertise in Alzheimer’s disease biology, CNS pharmaceutical drug discovery and development, and scientific excellence in the core discovery technologies that will drive the ADDD CENTER’s contributions and deliverables. A key advantage and differentiated strength of the proposed ADDD CENTER is the primary scientific coordination and administration through the Indiana University School of Medicine. Specifically, this concentrates a strong and long-standing commitment to neurodegenerative research through co-presence with the NIA-supported Indiana Alzheimer’s Disease Center under the direction of Dr. Andy Saykin, the MODEL-AD consortium under the direction of Dr. Bruce Lamb, and the Longitudinal Early Onset Alzheimer’s Disease (LEAD) study under the direction of Dr. Liana Apostolova. The Specific Aims of the ADDD CENTER are: 1. Create a dynamic portfolio of well-characterized AD drug discovery targets representing novel intervention hypotheses that capitalize on significant investments in basic research and emerging disease understanding. 2. Perform advanced pre-clinical target validation and enablement studies to prioritize the best opportunities for therapeutic discovery. 3. Create high-quality and well-characterized lead molecules for prioritized targets that meet rigorous milestone criteria and are valued opportunities for further translational investment. 4. Create a robust and flexible data sharing platform to enable global researchers with data and target enablement packages to expand on the work of the ADDD CENTER.