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Updated: Mar 11, 2026
Obtaining Human Microglia from Adult Human Brain Tissue
Published on: August 30, 2020
Microglia show altered morphology and reduced arborization in human brain during aging and Alzheimer's disease
Danielle S Davies1,2, Jolande Ma1,2, Thuvarahan Jegathees1
1Brain and Mind Centre, The University of Sydney, New South Wales, Australia.
Abstract:
Changes in microglia function are involved in Alzheimer's disease (AD) for which ageing is the major risk factor. We evaluated microglial cell process morphologies and their gray matter coverage (arborized area) during ageing and in the presence and absence of AD pathology in autopsied human neocortex. Microglial cell processes were reduced in length, showed less branching and reduced arborized area with aging (case range 52-98 years). This occurred during normal ageing and without microglia dystrophy or changes in cell density. There was a larger reduction in process length and arborized area in AD compared to aged-matched control microglia. In AD cases, on average, 49%-64% of microglia had discontinuous and/or punctate Iba1 labeled processes instead of continuous Iba1 distribution. Up to 16% of aged-matched control microglia displayed discontinuous or punctate features. There was no change in the density of microglial cell bodies in gray matter during ageing or AD. This demonstrates that human microglia show progressive cell process retraction without cell loss during ageing. Additional changes in microglia occur with AD including Iba1 protein puncta and discontinuity. We suggest that reduced microglial arborized area may be an aging-related correlate of AD in humans. These variations in microglial cells during ageing and in AD could reflect changes in neural-glial interactions which are emerging as key to mechanisms involved in ageing and neurodegenerative disease.
Insights
Aging human microglia retract their processes, reducing gray matter coverage. Alzheimer's disease (AD) exacerbates this process retraction and causes further changes in microglia, suggesting a role in neurodegeneration.
Area of Science:
- Neuroscience
- Aging Research
- Alzheimer's Disease Pathogenesis
Background:
- Microglia, the immune cells of the brain, are increasingly implicated in Alzheimer's disease (AD), with aging being the primary risk factor for AD.
- Understanding age-related changes in microglia is crucial for deciphering their role in neurodegenerative diseases.
Purpose of the Study:
- To investigate microglial cell process morphology and gray matter coverage during aging and in Alzheimer's disease (AD).
- To determine if aging-induced microglial changes correlate with AD pathology.
Main Methods:
- Analysis of microglial cell process length, branching, and arborized area in human neocortex from autopsied individuals across a wide age range (52-98 years).
- Comparison of microglial morphology in normal aging individuals versus those with AD pathology.
- Assessment of microglial cell density and Iba1 (ionized calcium-binding adapter molecule 1) distribution in processes.
Main Results:
- Microglial processes showed reduced length, branching, and arborized area with aging, independent of cell density or dystrophy.
- Individuals with AD exhibited a more pronounced reduction in microglial process length and arborized area compared to age-matched controls.
- A significant percentage of microglia in AD cases (49%-64%) displayed discontinuous or punctate Iba1-labeled processes, a feature observed less frequently in controls (up to 16%).
- No changes in microglial cell body density were observed in gray matter during aging or in AD.
Conclusions:
- Human microglia undergo progressive process retraction and reduced gray matter coverage during aging, without a decrease in cell numbers.
- Alzheimer's disease is associated with additional microglial alterations, including Iba1 puncta and process discontinuity.
- Reduced microglial arborized area may serve as an aging-related biomarker for AD in humans.
- These age- and AD-associated microglial changes highlight the importance of neural-glial interactions in aging and neurodegeneration.
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