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Microglial heterogeneity in aging and Alzheimer's disease: Is sex relevant?
Charlotte Isabelle Delage1, Eva Šimončičová1, Marie-Ève Tremblay2
1Division of Medical Sciences, University of Victoria, Victoria, Canada.
Abstract:
Neurodegenerative diseases and their associated cognitive decline are known to be more prevalent during aging. Recent evidence has uncovered the role of microglia, the immunocompetent cells of the brain, in dysfunctions linked to neurodegenerative diseases such as is Alzheimer's disease (AD). Similar to other pathologies, AD is shown to be sex-biased, with females being more at risk compared to males. While the mechanisms driving this prevalence are still unclear, emerging data suggest the sex differences present in microglia throughout life might lead to different responses of these cells in both health and disease. Furthermore, microglial cells have recently been recognized as a deeply heterogeneous population, with multiple subsets and/or phenotypes stemming from diverse parameters such as age, sex or state of health. Therefore, this review discusses microglial heterogeneity during aging in both basal conditions and AD with a focus on existing sex differences in this process.
Insights
Microglia, the brain's immune cells, play a role in neurodegenerative diseases like Alzheimer's. This review examines how microglial heterogeneity and sex differences impact aging and Alzheimer's disease.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Neurodegenerative diseases, including Alzheimer's disease (AD), are more common with aging and exhibit a sex bias, with females at higher risk.
- Microglia, the brain's resident immune cells, are increasingly implicated in the pathogenesis of neurodegenerative conditions.
- Emerging evidence highlights the heterogeneity of microglial populations and potential sex-based differences in their function.
Purpose of the Study:
- To review the concept of microglial heterogeneity during aging.
- To explore sex differences in microglial function in both healthy aging and Alzheimer's disease.
- To synthesize current understanding of how these factors interact in neurodegeneration.
Main Methods:
- Literature review of recent studies on microglia, aging, sex differences, and Alzheimer's disease.
- Analysis of research investigating microglial phenotypes and heterogeneity.
- Synthesis of findings related to sex-based disparities in microglial responses.
Main Results:
- Microglia are not a uniform population; they exhibit diverse phenotypes influenced by age and sex.
- Sex differences in microglia may contribute to the higher prevalence of AD in females.
- Aging alters microglial characteristics, potentially exacerbating disease-related changes.
Conclusions:
- Microglial heterogeneity and sex differences are critical factors in understanding aging and Alzheimer's disease.
- Further research into sex-specific microglial biology is needed to develop targeted therapies.
- Addressing these differences could lead to more effective strategies for preventing and treating AD.
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