Dynamic Neuroimmune Profile during Mid-life Aging in the Female Brain and Implications for Alzheimer Risk

Aarti Mishra; Yuan Shang; Yiwei Wang; Eliza R Bacon; Fei Yin; Roberta D Brinton

doi:10.1016/j.isci.2020.101829

Dynamic Neuroimmune Profile during Mid-life Aging in the Female Brain and Implications for Alzheimer Risk

iScience. 2020 Nov 20;23(12):101829. doi: 10.1016/j.isci.2020.101829. eCollection 2020 Dec 18.

Authors

Aarti Mishra¹, Yuan Shang¹, Yiwei Wang¹, Eliza R Bacon², Fei Yin¹, Roberta D Brinton¹

Affiliations

¹ Center for Innovation in Brain Science, University of Arizona, Tucson, AZ 85719, USA.
² Department of Medical Oncology, Beckman Research Institute, City of Hope, Duarte, CA 91010, USA.

Abstract

Aging 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.

Keywords: Endocrinology; Immunology; Neuroscience; Transcriptomics.

Abstract

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