摘要：SummaryAging and endocrine transition states can significantly impact inflammation across organ systems. Neuroinflammation is well documented in Alzheimer disease (AD). Herein, we investigated neuroinflammation 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 neuroimmune activation. Translationally, these findings have implications for therapeutic interventions during mid-life to decrease late-onset AD risk.Graphical AbstractDisplay OmittedHighlights•Neuroimmune profile was dynamic across aging transitions in female brain•Microglial reactivity was spatially dependent and most evident in white matter•Neuroimmune signature of perimenopause parallels neurodegenerative profile•Discovery outcomes profiles human hippocampal immune microarray profile in womenNeuroscience; Immunology; Endocrinology; Transcriptomics
