PROJECT SUMMARY – ANIMAL CORE Each year ~1.5 million American women enter into the perimenopause, a neuroendocrine transition state unique to the female. 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). 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. Animal Core contributes to meeting P3 goals through provision of veterinary service and support to Projects 1–3. To achieve its mission, Animal Core will maintain and track animals using the Electronic Veterinary Management Platform, provide humanized APOE Perimenopause Animal Model (PAM) model to projects, conduct physiological and behavioral assessment, perform intervention regimen, and conduct tissue collection for analyses by Analytic Core and/or individual Projects across the entire Perimenopause Program Project. During previous P3 periods, we developed a rodent model of human perimenopause that recapitulates key features of human perimenopause. Using this model, our investigation provided new mechanistic insights into the biological transformations in chronological and endocrinological aging in female brains. Animal Core will continue to serve as an instrumental resource to achieve the Program Project’s overall mission and aims by providing scientifically validated and translationally relevant animal models. Outcomes of Animal Core support will enable achieving the Perimenopause in Brain Aging and Alzheimer’s Disease Program Project mission and aims through the veterinary care and testing capabilities it has developed Research proposed herein addresses strategic goals of the National Institutes on Aging’s 2016: Aging Well in the 21st Century: Strategic Directions for Research on Aging, specifically Goals A1, 2, 3, 7, 8 & 11 and Goals D1, 2, & 4.