CORE A- SUMMARY/ABSTRACT Our ultimate goal of this program grant is to gain a better understanding of the heterogeneous pathogenesis of AD and how it is influenced by apolipoprotein (apo) E isotypes, using human tissue, with correlations to findings in various AD models, using proteomic and other methods which we have recently developed. In particular we are focusing on the differential role apolipoprotein E (apoE) isoforms play in: 1) AD plaque and vessel amyloid development (Project 1); 2) therapeutic approaches that target the Aβ/apoE interaction (Project 2); 3) responses to therapeutic immunomodulation targeting abnormal conformation (Project 3). The Administrative Core (Core A) is charged with ensuring the success of this research proposal. The Aims are: Aim 1. Provide administrative structure and fiscal oversight for the program project grant. Aim 2. Organize regular meetings of the Executive Committee (EC) composed of Project and Core Leaders and other key personnel to assist in scientific administration and to facilitate integration and continuing progress on research aims. Aim 3. Coordinate with the bioinformatics/statistical/data management Core D to ensure optimal data utilization and scientific rigor for the Program Project. Aim 4. Interact closely with the External Advisory Committee and Internal Advisory Board, and conduct regular meetings of both. The External Advisory Committee and Internal Advisory Board will provide scientific advice and guidance for all research projects. Aim 5. Report progress to NIH and ensure compliance with the NIH Public Access policy. Aim 6. Promote education on AD and related disorders, and facilitate P01 scientists’ participation in education to researchers, clinicians and patients/caregivers.