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Inflammation in dementia with Lewy bodies

Inflammation in dementia with Lewy bodies
Inflammation in dementia with Lewy bodies
Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). The profile of inflammation in AD has been extensively researched in recent years, with evidence that chronic peripheral inflammation in midlife increases the risk of late-onset AD, and data supporting inflammation being associated with disease progression. In contrast, our understanding of the role of inflammation in DLB is less developed. Most research to date has examined inflammation in related disorders, such as Parkinson's disease, but there is now a growing range of literature examining inflammation in DLB itself. We present a review of the literature in this field, exploring a range of research methodologies including those quantifying markers of inflammation in cerebrospinal fluid, peripheral blood, post-mortem brain tissue, and using neuroimaging and preclinical data. Our review reveals evidence from PET imaging and peripheral blood analysis to support an increase in cerebral and peripheral inflammation in mild or prodromal DLB, that dissipates with disease progression. We present evidence from post-mortem brain tissue and pre-clinical studies that indicate α-synuclein directly promotes inflammation, but that also support the presence of AD co-pathology as an important factor in the profile of neuroinflammation in DLB. We propose that specific markers of inflammation may play a sentinel role in the mild stage of the disease, particularly when combined with AD pathology. We advocate further examination of the profile of inflammation in DLB through robust longitudinal studies, to enhance our understanding of the pathogenesis of the disease. The goal should be to utilise future results to develop a composite biomarker to aid diagnosis of DLB, and to potentially identify novel therapeutic targets.
Cytokines, Dementia with Lewy bodies, Inflammation, Microglia, Synuclein
0969-9961
Amin, Jay
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Erskine, Daniel
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Donaghy, Paul C
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Surendranathan, Ajenthan
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Swann, Peter
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Kunicki, Amy P.
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Boche, Delphine
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Holmes, Clive
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McKeith, Ian G.
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O'Brien, John T
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Teeling, Jessica L
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Thomas, Alan J.
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Amin, Jay
b91805fc-c9fe-4504-94c6-49189e512458
Erskine, Daniel
05c5e29b-e78a-4bcb-a171-afd2776d47e9
Donaghy, Paul C
78739085-4442-4ac2-b09d-d233608600bc
Surendranathan, Ajenthan
236d29f1-ce36-46ea-8c23-ddbf4fb050e8
Swann, Peter
e135cab9-ebd6-4038-be68-e2f358c4273a
Kunicki, Amy P.
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Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Holmes, Clive
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McKeith, Ian G.
d10591da-19e5-4a1c-8d40-c175495bfbdb
O'Brien, John T
245c03f3-bf8c-416d-892e-cdc202d960a6
Teeling, Jessica L
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Thomas, Alan J.
fbb6de4d-6b86-4370-a923-b9ade0383a32

Amin, Jay, Erskine, Daniel, Donaghy, Paul C, Surendranathan, Ajenthan, Swann, Peter, Kunicki, Amy P., Boche, Delphine, Holmes, Clive, McKeith, Ian G., O'Brien, John T, Teeling, Jessica L and Thomas, Alan J. (2022) Inflammation in dementia with Lewy bodies. Neurobiology of Disease, 168 (6), [105698]. (doi:10.1016/j.nbd.2022.105698).

Record type: Review

Abstract

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). The profile of inflammation in AD has been extensively researched in recent years, with evidence that chronic peripheral inflammation in midlife increases the risk of late-onset AD, and data supporting inflammation being associated with disease progression. In contrast, our understanding of the role of inflammation in DLB is less developed. Most research to date has examined inflammation in related disorders, such as Parkinson's disease, but there is now a growing range of literature examining inflammation in DLB itself. We present a review of the literature in this field, exploring a range of research methodologies including those quantifying markers of inflammation in cerebrospinal fluid, peripheral blood, post-mortem brain tissue, and using neuroimaging and preclinical data. Our review reveals evidence from PET imaging and peripheral blood analysis to support an increase in cerebral and peripheral inflammation in mild or prodromal DLB, that dissipates with disease progression. We present evidence from post-mortem brain tissue and pre-clinical studies that indicate α-synuclein directly promotes inflammation, but that also support the presence of AD co-pathology as an important factor in the profile of neuroinflammation in DLB. We propose that specific markers of inflammation may play a sentinel role in the mild stage of the disease, particularly when combined with AD pathology. We advocate further examination of the profile of inflammation in DLB through robust longitudinal studies, to enhance our understanding of the pathogenesis of the disease. The goal should be to utilise future results to develop a composite biomarker to aid diagnosis of DLB, and to potentially identify novel therapeutic targets.

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Inflammation in DLB review revised v6 - Accepted Manuscript
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Inflammation in DLB review revised v6 - Accepted Manuscript
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Accepted/In Press date: 15 March 2022
e-pub ahead of print date: 18 March 2022
Published date: 15 June 2022
Additional Information: Funding Information: JOB has acted as a consultant for TauRx, Eisai, Novo Nordisk , Biogen and GE Healthcare and received grant support from Avid/Lilly, Merck and Alliance Medical . Funding Information: JT received grant support from Cortexyme, Medimmune/AstraZeneca and Therini. Funding Information: JOB is supported by the NIHR Cambridge Biomedical Research Centre . Funding Information: AJT is supported by NIHR Newcastle Biomedical Research Centre and Brains for Dementia Research. Funding Information: DE is supported by an Alzheimer's Research UK Fellowship ( ARUK-RF2018C-005 ). Funding Information: PD is supported by the NIHR Newcastle Biomedical Research Centre. Publisher Copyright: © 2022 The Authors Copyright: Copyright 2022 Elsevier B.V., All rights reserved.
Keywords: Cytokines, Dementia with Lewy bodies, Inflammation, Microglia, Synuclein

Identifiers

Local EPrints ID: 456204
URI: http://eprints.soton.ac.uk/id/eprint/456204
ISSN: 0969-9961
PURE UUID: 5f72ef0f-a2ea-421f-a770-bf2f1920b2a9
ORCID for Jay Amin: ORCID iD orcid.org/0000-0003-3792-0428
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for Jessica L Teeling: ORCID iD orcid.org/0000-0003-4004-7391

Catalogue record

Date deposited: 26 Apr 2022 16:50
Last modified: 31 Jan 2023 02:40

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Contributors

Author: Jay Amin ORCID iD
Author: Daniel Erskine
Author: Paul C Donaghy
Author: Ajenthan Surendranathan
Author: Peter Swann
Author: Amy P. Kunicki
Author: Delphine Boche ORCID iD
Author: Clive Holmes ORCID iD
Author: Ian G. McKeith
Author: John T O'Brien
Author: Alan J. Thomas

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