PROJECT SUMMARY (APOE U19 Core A: Administrative Core) The Administrative Core will lead this U19 project by providing administrative, fiscal, and scientific oversight and promoting synergy of all Cores and Projects to address the ApoE Cascade Hypothesis. Core A will serve several functions to facilitate the scientific objectives and rigor of this U19. It will also serve the broader scientific community by sharing knowledge, resources, and datasets through a web portal and by promoting collaboration through an annual ApoE Symposium. Core A will cooperate fully with NIA initiatives with a dedicated leadership team and administrative personnel with relevant experience. As the Co-PIs of this U19 project and Co-Leaders of Core A, Drs. Guojun Bu (Mayo Clinic Jacksonville) and David Holtzman (Washington University in St. Louis) are recognized leaders in the apoE field; each has more than 25 years of experience studying apoE and apoE receptors as they relate to the pathogenesis of AD and other aging- related conditions. Drs. Bu and Holtzman have a long history of collaboration and are well positioned to share leadership roles for this U19 program at the two coordinating institutions. They also have strong leadership experience each serving as a Department Chair and an Associate Director of Alzheimer’s Disease Research Center at their respective institution. Together with Dr. Alison Goate, who will serve as the Site-PI at Icahn School of Medicine at Mount Sinai, they will ensure integration and synergy across the U19 by pursuing the following aims: Aim 1: Provide administrative structure, fiscal oversight, and site coordination for the U19 program. Aim 2: Assume responsibility for the quality control of the U19 activities by ensuring responsible conduct of research, rigor, and reproducibility of research practices, and by ensuring compliance with all internal and external regulatory requirements. Promote and track open-access publications and facilitate submission of progress reports to NIH. Aim 3: Promote the scientific direction and integration of the U19 components by organizing meetings of the Internal Steering Committee and External Advisory Committee. Aim 4: Develop and maintain an apoE website what will serve as knowledge portal, and resource and data sharing platform. Aim 5: Organize Annual ApoE Symposium for U19 investigators as well as the broader scientific community to interact and share research findings. These innovative aims will ensure that the robust and rigorous efforts by the U19 team investigators will lead to new discoveries to inform therapeutic strategies.