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.
Highlights
Microglia are the brain immune cells and their function is highly dependent on cell motility
The aim of the present study was to assess in detail and in a quantitative manner in largest cohorts of Alzheimer’s disease (AD) and control brains, several features of the microglial morphology imaged from human brain and compare the information provided by the two-dimensional (2D) and three-dimensional (3D) approaches
Comparison of iAD cases with the control group showed the amoeboid microglial population to be modestly increased in iAD (13 vs. 21 amoeboid cells/10 fields, P = 0.046) (Fig. 1)
Summary
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, impacting on the microglial function. 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. Aβ removal by immunotherapy leads to increased ramified microglia, implying that the cells retain plasticity in an aged disease brain meriting further investigation. Microglia are a key component of the resident immune system of the brain They are, to some extent, similar to macrophages in their expression profile and in their behaviour and functions. The aim of the present study was to assess in detail and in a quantitative manner in largest cohorts of AD and control brains, several features of the microglial morphology imaged from human brain and compare the information provided by the two-dimensional (2D) and three-dimensional (3D) approaches. Microglial morphological changes was explored after Aβ immunotherapy, using our unique group of AD patients immunised against Aβ4210
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