Microglial morphology in Alzheimer's disease and after Aβ immunotherapy
Microglial morphology in Alzheimer's disease and after Aβ immunotherapy
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.
Aged, Aged, 80 and over, Alzheimer Disease/immunology, Amyloid beta-Peptides/immunology, Amyloid beta-Protein Precursor/immunology, Brain/metabolism, Female, Humans, Immunotherapy/methods, Male, Microglia/metabolism, Neurofibrillary Tangles/metabolism, Tissue Banks
15955
Franco-Bocanegra, Diana K
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Gourari, Yamina
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McAuley, Ciaran
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Chatelet, David S
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Johnston, David A
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Nicoll, James A R
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Boche, Delphine
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Franco-Bocanegra, Diana K
ad8042ca-0800-495e-a32c-1bdca88aacaa
Gourari, Yamina
b9112fae-1ffb-4b6a-ae7c-0c09981e0779
McAuley, Ciaran
39aecc0b-2c2e-48fb-ac83-ecae54d7d626
Chatelet, David S
6371fd7a-e274-4738-9ccb-3dd4dab32928
Johnston, David A
b41163c9-b9d2-425c-af99-2a357204014e
Nicoll, James A R
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Franco-Bocanegra, Diana K, Gourari, Yamina, McAuley, Ciaran, Chatelet, David S, Johnston, David A, Nicoll, James A R and Boche, Delphine
(2021)
Microglial morphology in Alzheimer's disease and after Aβ immunotherapy.
Scientific Reports, 11 (1), .
(doi:10.1038/s41598-021-95535-0).
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.
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s41598-021-95535-0
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e-pub ahead of print date: 5 August 2021
Additional Information:
© 2021. The Author(s).
Keywords:
Aged, Aged, 80 and over, Alzheimer Disease/immunology, Amyloid beta-Peptides/immunology, Amyloid beta-Protein Precursor/immunology, Brain/metabolism, Female, Humans, Immunotherapy/methods, Male, Microglia/metabolism, Neurofibrillary Tangles/metabolism, Tissue Banks
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Local EPrints ID: 458149
URI: http://eprints.soton.ac.uk/id/eprint/458149
ISSN: 2045-2322
PURE UUID: 63b82dff-8037-431c-a45e-fff58b7d8fd4
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Date deposited: 29 Jun 2022 17:17
Last modified: 17 Nov 2022 02:38
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Author:
Diana K Franco-Bocanegra
Author:
Yamina Gourari
Author:
Ciaran McAuley
Author:
David S Chatelet
Author:
David A Johnston
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