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Updated: Jul 14, 2026
Obtaining Human Microglia from Adult Human Brain Tissue
Published on: August 30, 2020
Human Microglial Molecular Alterations in Aging and Alzheimer's Disease
Karol Ann T Baldo1,2, Elisa Gozlan3, Emmanuel O Chidebe4
1School of Medical Sciences, Faculty of Health, University of Victoria, Victoria, BC V8P 5C2, Canada.
Abstract:
Microglia, the resident innate immune cells of the central nervous system, are central players in brain development, healthy aging, and degenerative pathology, including Alzheimer's disease (AD). Aging is a major risk factor for AD, and various studies have identified alterations in microglial molecular signatures and morphological patterns that overlap with microglial states during aging. However, the mechanisms underlying the divergence of aging trajectories toward disease remain unclear. Thus, understanding the molecular changes in microglia during aging and AD pathology is crucial to elucidating the mechanisms that drive disease progression. In this review, we examine current advances in understanding the phenotypic alterations in human microglia, highlighting gene signatures and morphological changes that may aid in defining microglia's molecular and functional programs in healthy aging and over the course of AD. We further explore the roles of oxidative stress and cellular senescence in driving the development of a chronic reactive state in microglia during aging, which may also contribute to the complex process underlying the onset and progression of AD pathology. This review highlights the advancements in therapeutic strategies focused on targeting pertinent pathological microglial changes during aging and in disease to mitigate the AD neurodegenerative process.
Insights
Microglia, the brain's immune cells, change during aging and Alzheimer's disease (AD). Understanding these microglial alterations is key to developing new AD therapies.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are key immune cells in the central nervous system, vital for brain health and disease.
- Aging is a significant risk factor for Alzheimer's disease (AD), with observed changes in microglia mirroring aging states.
- The precise mechanisms driving divergent aging paths toward AD remain elusive.
Purpose of the Study:
- To review current knowledge on human microglial phenotypic changes in aging and AD.
- To explore molecular and functional shifts in microglia during healthy aging and AD progression.
- To investigate the roles of oxidative stress and cellular senescence in microglial aging and AD.
Main Methods:
- Review of existing literature on microglial alterations in aging and AD.
- Analysis of gene signatures and morphological changes in human microglia.
- Exploration of cellular mechanisms like oxidative stress and senescence.
Main Results:
- Aging and AD induce overlapping alterations in microglial molecular signatures and morphology.
- Oxidative stress and cellular senescence contribute to a chronic reactive microglial state during aging.
- These microglial changes are implicated in the onset and progression of AD pathology.
Conclusions:
- Understanding microglial changes in aging and AD is crucial for elucidating disease mechanisms.
- Targeting pathological microglial alterations offers potential therapeutic strategies for AD.
- Further research into microglial programs can guide the development of AD mitigation treatments.
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