PROJECT ABSTRACT – ADMINISTRATIVE CORE A The mission of the Perimenopause in Brain Aging and Alzheimer’s disease (P3) is to discover biological transformations in brain that occur during the perimenopausal transition that lead to endophenotypes predictive of risk for Alzheimer’s disease (AD). Each year ~1.5 million American women enter into the perimenopause, a neuroendocrine transition state unique to the female. Herein, we focus on the neuro-immune system as a key driver of chronological and endocrinological aging that occurs in the midlife female brain. Our goals are to identify the mechanisms by which these transformations occur and to translate these discoveries into strategies to prevent conversion to an at-Alzheimer's-risk phenotype. The P3 is a mission focused, synergistic and integrated program of research that spans molecular, cellular, systems biology, population and clinical science. To achieve P3 research goals, Administrative Core A (Core A) sets a strategic vision and provides structural organization and resources to facilitate research endeavors and integration across all Projects and Cores. Experts in the aging brain, Alzheimer’s disease, molecular and cellular bioenergetics, metabolic and immune systems of biology, medical informatics, advanced human brain imaging and research will advance P3 research. To achieve the P3 mission, Core A will execute three Specific Aims. In Aim1, we set a clear strategic vision and provide tactical management and support to achieve Project, Core and Program-wide goals. Aim 1 will provide and enable program-wide management of research productivity, resources, and integration through proactive project management, Program Sync Meetings, Fiscal Management, Data Management and Publication of research findings. Aim 1 will also serve as a research training hub for pre-doctoral (T32AG061897), post-doctoral (T32AG044402), Navajo undergraduate (R25NS107185) and clinical (P30AG019610) fellows. In Aim 2, Core A will enable P3-wide integration of resources, conduct of research and data analytics. Activities include deploying transparent and effective program-wide collaboration and communication tools; including: (i) a cloud-based veterinary management system, (ii) common electronic laboratory notebook, and (iii) data repository and analysis hub. In Aim 3 Core A will enable P3-wide Integrated Data Fusion and Systems Biology Analysis. Activities include: (i) Integration of data (fusion) for computational analyses, (ii) executing cross-cutting computational systems biology analyses, and (iii) providing program-wide statistical, bioinformatic design to ensure full data harmonization and integration to facilitate the sharing of data and expedite translation. Outcomes of Administrative Core will enable achieving P3 goals through strategic, tactical and analytic support to all Projects and Cores. The Perimenopause in Brain Aging and Alzheimer’s Disease program of research addresses key strategic goals of the National...