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Journal Article Ppublish 8 citations

PubMed: 40247152 DOI: 10.1002/alz.14603

Sex- and region-dependent neuroinflammation in Alzheimer's disease.

Alzheimers Dement 21(4):e14603

Authors: Maricedes Acosta-Martínez, Vanessa Carter, Aviram Nessim, Radha Panchal, Dora John, Jasbeer Dhawan, Thomas G Beach, Geidy E Serrano, Erin E Sundermann, Anat Biegon

Affiliations

  • Department of Physiology & Biophysics, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA.
  • Department of Radiology, Renaissance School of Medicine at Stony Brook University, Stony Brook, New York, USA.
  • Banner Sun Banner Health Research Institute, Sun City, Arizona, USA.
  • Department of Psychiatry, University of California, San Diego, California, USA.

Abstract

INTRODUCTION

Despite known sex differences in immune function and Alzheimer's disease (AD), most studies of neuroinflammation in AD have not been analyzed by sex.

METHODS

We performed quantitative in vitro autoradiography of hippocampus, entorhinal cortex, and parietal cortex using [H]-PK1195 and [F]-T807. Proinflammatory microRNA (miRNA) expression in parietal cortex was measured by quantitative polymerase chain reaction (qPCR).

RESULTS

We found significant, region-dependent elevations of translocator protein (TSPO) density in AD relative to cognitively normal (CN) and mild cognitive impairment (MCI) in women but not men. Density of tau was increased in AD relative to CN and MCI in both sexes, but only women showed a significant positive correlation between tau and TSPO density. The expression of proinflammatory miRNAs was also significantly increased in AD versus CN or MCI women but not men.

DISCUSSION

Women are more susceptible than men to AD/tau-related neuroinflammation, supporting a sex-specific re-examination of the effects of neuroinflammation-targeting interventions in AD.

HIGHLIGHTS

We show that neuroinflammation in Alzheimer's disease (AD) is modulated by sex in a region-specific manner. Neuroinflammation was highest in the subiculum and significant only in women. Inflammatory microRNAs (miRNAs) increased in the parietal cortex of women, but not men, with AD. Deposition of tau was highest in the entorhinal cortex and significant in both sexes. Density of tau and TSPO was positively and significantly correlated only in AD women.

MeSH

Hippocampus, Dementia, Entorhinal Cortex, Alzheimer Disease, Micrornas, Cognitive Dysfunction, Parietal Lobe, Sex

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