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Updated: Oct 25, 2025
Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
Microglial morphology in Alzheimer's disease and after Aβ immunotherapy
Diana K Franco-Bocanegra1, Yamina Gourari1, Ciaran McAuley1
1Clinical Neurosciences, Clinical and Experimental Sciences School, Faculty of Medicine, University of Southampton, Southampton, UK.
Abstract:
Microglia are the brain immune cells and their function is highly dependent on cell motility. It was hypothesised that morphological variability leads to differences in motility, ultimately impacting on the microglial function. Here, we assessed microglial morphology in 32 controls, 44 Alzheimer's disease (AD) cases and 16 AD cases from patients immunised against Aβ42 (iAD) using 2D and 3D approaches. Our 2D assessment showed an increased number of microglia in iAD vs. AD (P = 0.032) and controls (P = 0.018). Ramified microglia were fewer in AD vs. controls (P = 0.041) but increased in iAD compared to AD (P < 0.001) and controls (P = 0.006). 3D reconstructions highlighted larger cell bodies in AD vs. controls (P = 0.049) and increased total process length in iAD vs. AD (P = 0.032), with negative correlations detected for pan-Aβ load with total process length (P < 0.001) in AD and number of primary processes (P = 0.043) in iAD. In summary, reactive/amoeboid microglia are the most represented population in the aged human brain. AD does not affect the number of microglia, but the ramified population is decreased adopting a more reactive morphology. Aβ removal by immunotherapy leads to increased ramified microglia, implying that the cells retain plasticity in an aged disease brain meriting further investigation.
Insights
Microglia morphology changes with Alzheimer's disease (AD). Immunotherapy against amyloid-beta (Aβ) in AD patients restores ramified microglia, indicating brain immune cell plasticity.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the primary immune cells in the brain, crucial for neuronal health.
- Microglial function is intrinsically linked to their motility and morphology.
- Morphological changes in microglia are hypothesized to correlate with altered motility and function, particularly in neurodegenerative diseases.
Purpose of the Study:
- To investigate the morphological characteristics of microglia in controls, Alzheimer's disease (AD) patients, and AD patients treated with Aβ42 immunotherapy (iAD).
- To determine if microglial morphology correlates with disease state and Aβ pathology.
- To assess the impact of Aβ immunotherapy on microglial morphology and plasticity.
Main Methods:
- Comparative analysis of microglial morphology using 2D and 3D imaging techniques.
- Quantification of microglial numbers and morphological types (e.g., ramified, reactive/amoeboid).
- Correlation analysis between microglial morphology and Aβ load in brain tissue.
Main Results:
- Alzheimer's disease (AD) brains showed decreased ramified microglia and larger cell bodies compared to controls.
- Immunotherapy against Aβ (iAD) resulted in an increased number of microglia and a higher proportion of ramified microglia compared to AD and control groups.
- Aβ load negatively correlated with microglial process length and number of primary processes in AD and iAD groups, respectively.
Conclusions:
- Reactive/amoeboid microglia are prevalent in the aged human brain.
- AD pathology alters microglial morphology, reducing ramified forms and increasing reactive states.
- Aβ immunotherapy promotes a shift towards ramified microglia, demonstrating their plasticity in an aged, diseased brain.
