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Neuroinflammation in dementia with Lewy bodies: a human post-mortem study

Neuroinflammation in dementia with Lewy bodies: a human post-mortem study
Neuroinflammation in dementia with Lewy bodies: a human post-mortem study
Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer’s disease (AD). It is now established that cerebral inflammation has a key role in the aetiology and progression of AD, but this has yet to be confirmed in DLB. We aimed to determine the neuroinflammatory profile in the cerebral cortex of a large cohort of DLB cases. Thirty post-mortem confirmed DLB cases and twenty-nine matched controls were immunolabelled (Brodmann area 21) and quantified for: neuropathology—αSYN, Aβ, P-tau; microglial phenotype—Iba1, HLA-DR, CD68, FcƴR (CD64, CD32a, CD32b, CD16); presence of T lymphocytes—CD3; and anti-inflammatory markers—IL4R, CHI3L1. Status spongiosis, as a marker of neuropil degeneration, was quantified using Haematoxylin and Eosin staining. We found no significant difference between groups in protein load for Iba1, HLA-DR, CD68, CD64, CD32b, IL4R, or CHI3L1, despite increased neuropathology in DLB. CD32a load was significantly lower, and CD16 load higher, in DLB compared with controls. There was no difference in status spongiosis between groups. Significantly more DLB cases than controls showed T-lymphocyte recruitment. Overall, we conclude that microglial activation is not a prominent feature of DLB, and that this may be associated with the relatively modest neuropil degeneration observed in DLB. Our findings, based on the largest post-mortem cohort to date exploring neuroinflammation in DLB, demonstrate a dissociation between protein deposition, neurodegeneration and microglial activation. The relative preservation of cortical structures in DLB suggests the dementia could be more amenable to potential therapies.
1-11
Amin, Jay
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Holmes, Clive
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Dorey, Robert B.
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Tommasino, Emmanuele
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Reis Casal, Yuri
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Williams, Daisy
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Dupuy, Charles
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Nicoll, James
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Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Dorey, Robert B.
8d4b042f-1659-4e76-99c2-23cde78ca4f5
Tommasino, Emmanuele
842485c9-3bb2-4872-94a2-627b034ac5d5
Reis Casal, Yuri
46fb5376-af2a-4dad-b918-bffd44b384b3
Williams, Daisy
bca59d42-e48b-4073-9d68-79f0746def91
Dupuy, Charles
5d0b7ab6-c37e-43c9-aa93-2b0e2a6e5e6c
Nicoll, James
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61

Amin, Jay, Holmes, Clive, Dorey, Robert B., Tommasino, Emmanuele, Reis Casal, Yuri, Williams, Daisy, Dupuy, Charles, Nicoll, James and Boche, Delphine (2020) Neuroinflammation in dementia with Lewy bodies: a human post-mortem study. Translational Psychiatry, 10 (1), 1-11, [267]. (doi:10.1038/s41398-020-00954-8).

Record type: Article

Abstract

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer’s disease (AD). It is now established that cerebral inflammation has a key role in the aetiology and progression of AD, but this has yet to be confirmed in DLB. We aimed to determine the neuroinflammatory profile in the cerebral cortex of a large cohort of DLB cases. Thirty post-mortem confirmed DLB cases and twenty-nine matched controls were immunolabelled (Brodmann area 21) and quantified for: neuropathology—αSYN, Aβ, P-tau; microglial phenotype—Iba1, HLA-DR, CD68, FcƴR (CD64, CD32a, CD32b, CD16); presence of T lymphocytes—CD3; and anti-inflammatory markers—IL4R, CHI3L1. Status spongiosis, as a marker of neuropil degeneration, was quantified using Haematoxylin and Eosin staining. We found no significant difference between groups in protein load for Iba1, HLA-DR, CD68, CD64, CD32b, IL4R, or CHI3L1, despite increased neuropathology in DLB. CD32a load was significantly lower, and CD16 load higher, in DLB compared with controls. There was no difference in status spongiosis between groups. Significantly more DLB cases than controls showed T-lymphocyte recruitment. Overall, we conclude that microglial activation is not a prominent feature of DLB, and that this may be associated with the relatively modest neuropil degeneration observed in DLB. Our findings, based on the largest post-mortem cohort to date exploring neuroinflammation in DLB, demonstrate a dissociation between protein deposition, neurodegeneration and microglial activation. The relative preservation of cortical structures in DLB suggests the dementia could be more amenable to potential therapies.

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Neuroinflammation in DLB for Translational Psychiatry - final - Accepted Manuscript
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Accepted/In Press date: 6 July 2020
e-pub ahead of print date: 3 August 2020
Published date: 3 August 2020

Identifiers

Local EPrints ID: 442950
URI: http://eprints.soton.ac.uk/id/eprint/442950
PURE UUID: 49a90923-2d24-4316-ae8e-eaf80b188b07
ORCID for Jay Amin: ORCID iD orcid.org/0000-0003-3792-0428
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for James Nicoll: ORCID iD orcid.org/0000-0002-9444-7246
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

Catalogue record

Date deposited: 04 Aug 2020 16:30
Last modified: 26 Nov 2021 03:03

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Contributors

Author: Jay Amin ORCID iD
Author: Clive Holmes ORCID iD
Author: Robert B. Dorey
Author: Emmanuele Tommasino
Author: Yuri Reis Casal
Author: Daisy Williams
Author: Charles Dupuy
Author: James Nicoll ORCID iD
Author: Delphine Boche ORCID iD

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