Emergence of Dynamic Neuro-Immune Profile During Mid-life Aging in the Female Brain: Implications for Alzheimer's Disease Risk [Hot flash]

Aging and endocrine transition states can significantly impact inflammation across organ systems. Neuroinflammation is a well-documented feature in Alzheimer's disease (AD). Herein, we investigated neuro-inflammation that emerges during mid-life aging, chronological and endocrinological, in the female brain as an early initiating mechanism driving AD risk later in life. Analyses were conducted in a translational rodent model of mid-life chronological and endocrinological aging followed by validation in transcriptomic profiles from women versus age-matched men. In the translational model, the neuroinflammatory profile of mid-life aging in females was endocrine and chronological state specific, dynamic, anatomically distributed and persistent. Microarray dataset analyses of aging human hippocampus indicated a sex difference in neuroinflammatory profile in which women exhibited a profile comparable to the pattern discovered in our translational rodent model, whereas age-matched men exhibited a profile consistent with low neuro-immune activation. Translationally, these findings have implications for therapeutic interventions during mid-life to decrease late-onset AD risk. Overall design: Female rats were aged to 6 months before OVX and followed with E2 estrogen or estrogen prevention treatments