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Updated: Nov 22, 2025
Obtaining Human Microglia from Adult Human Brain Tissue
Published on: August 30, 2020
Dystrophic microglia are associated with neurodegenerative disease and not healthy aging in the human brain
Ryan K Shahidehpour1, Rebecca E Higdon1, Nicole G Crawford1
1Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA; Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
Abstract:
Loss of physiological microglial function may increase the propagation of neurodegenerative diseases. Cellular senescence is a hallmark of aging; thus, we hypothesized age could be a cause of dystrophic microglia. Stereological counts were performed for total microglia, 2 microglia morphologies (hypertrophic and dystrophic) across the human lifespan. An age-associated increase in the number of dystrophic microglia was found in the hippocampus and frontal cortex. However, the increase in dystrophic microglia was proportional to the age-related increase in the total number of microglia. Thus, aging alone does not explain the presence of dystrophic microglia. We next tested if dystrophic microglia could be a disease-associated microglia morphology. Compared with controls, the number of dystrophic microglia was greater in cases with either Alzheimer's disease, dementia with Lewy bodies, or limbic-predominant age-related TDP-43 encephalopathy. These results demonstrate that microglia dystrophy, and not hypertrophic microglia, are the disease-associated microglia morphology. Finally, we found strong evidence for iron homeostasis changes in dystrophic microglia, providing a possible molecular mechanism driving the degeneration of microglia in neurodegenerative disease.
Insights
Cellular senescence in microglia, not aging alone, drives neurodegenerative disease progression. Dystrophic microglia, linked to iron imbalance, are a key indicator of Alzheimer's and related dementias.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Microglia, the brain's immune cells, are crucial for neurological health.
- Loss of microglial function is implicated in neurodegenerative disease propagation.
- Cellular senescence, a marker of aging, prompted investigation into age-related microglial changes.
Purpose of the Study:
- To investigate the relationship between aging, cellular senescence, and the development of dystrophic microglia.
- To determine if dystrophic microglia are associated with specific neurodegenerative diseases.
- To explore potential molecular mechanisms underlying microglial degeneration.
Main Methods:
- Stereological counts of total microglia and specific morphologies (hypertrophic, dystrophic) were performed across the human lifespan.
- Microglial morphology was compared between healthy controls and individuals with Alzheimer's disease, dementia with Lewy bodies, and TDP-43 encephalopathy.
- Iron homeostasis in dystrophic microglia was analyzed.
Main Results:
- An age-associated increase in total microglia was observed, with dystrophic microglia numbers increasing proportionally.
- Dystrophic microglia, but not hypertrophic microglia, were significantly increased in neurodegenerative disease cases compared to controls.
- Evidence suggests altered iron homeostasis in dystrophic microglia.
Conclusions:
- Aging alone does not solely account for the presence of dystrophic microglia.
- Microglial dystrophy is a disease-associated morphology, indicating a role in neurodegeneration.
- Iron dysregulation may be a key factor in the degeneration of microglia during neurodegenerative diseases.
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