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Peripheral immunophenotype in Dementia with Lewy bodies and Alzheimer’s disease: an observational clinical study

Peripheral immunophenotype in Dementia with Lewy bodies and Alzheimer’s disease: an observational clinical study
Peripheral immunophenotype in Dementia with Lewy bodies and Alzheimer’s disease: an observational clinical study
Background: Inflammation plays a key role in the aetiology and progression of Alzheimer’s disease (AD). However, the immunophenotype of the second most common neurodegenerative cause of dementia, dementia with Lewy bodies (DLB), remains unclear. To date there have been no studies examining peripheral inflammation in DLB using multiplex immunoassay and flow cytometry concomitantly. We hypothesised that, using blood biomarkers, DLB would show an increased proinflammatory profile compared with controls, and that there would be a distinct profile compared with AD.

Methods: 93 participants (31 with DLB, 31 with AD and 31 healthy older controls) completed a single study visit for neuropsychiatric testing and phlebotomy. Peripheral blood mononuclear cells were quantified for T and B cell subsets using flow cytometry, and serum cytokine concentrations were measured using multiplex immunoassay.

Results: We detected reduced relative numbers of helper T cells and reduced activation of B cells in DLB compared with AD. Additionally, interleukin (IL)-1β was detected more frequently in DLB and the serum concentration of IL-6 was increased compared with controls.

Conclusions: Peripheral inflammation is altered in DLB compared with AD, with T cell subset analysis supporting a possible shift towards senescence of the adaptive immune system in DLB. Furthermore, there is a proinflammatory signature of serum cytokines in DLB. Identification of this unique peripheral immunophenotype in DLB could guide development of an immune-based biomarker and direct future work exploring potential immune modulation as a novel treatment.
0022-3050
1219-1226
Amin, Jay
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Boche, Delphine
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Clough, Zoe
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Teeling, Jessica
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Williams, Anthony
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Gao, Yifang
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Chudley, Lindsey
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Lau, Laurie
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Smith, Florence
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Harris, Scott
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Holmes, Clive
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Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Clough, Zoe
06b0b5fd-881d-4959-a048-2d006856990d
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Williams, Anthony
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Gao, Yifang
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Chudley, Lindsey
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Lau, Laurie
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Smith, Florence
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Harris, Scott
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Holmes, Clive
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Amin, Jay, Boche, Delphine, Clough, Zoe, Teeling, Jessica, Williams, Anthony, Gao, Yifang, Chudley, Lindsey, Lau, Laurie, Smith, Florence, Harris, Scott and Holmes, Clive (2020) Peripheral immunophenotype in Dementia with Lewy bodies and Alzheimer’s disease: an observational clinical study. Journal of Neurology, Neurosurgery & Psychiatry, 91 (11), 1219-1226. (doi:10.1136/jnnp-2020-323603).

Record type: Article

Abstract

Background: Inflammation plays a key role in the aetiology and progression of Alzheimer’s disease (AD). However, the immunophenotype of the second most common neurodegenerative cause of dementia, dementia with Lewy bodies (DLB), remains unclear. To date there have been no studies examining peripheral inflammation in DLB using multiplex immunoassay and flow cytometry concomitantly. We hypothesised that, using blood biomarkers, DLB would show an increased proinflammatory profile compared with controls, and that there would be a distinct profile compared with AD.

Methods: 93 participants (31 with DLB, 31 with AD and 31 healthy older controls) completed a single study visit for neuropsychiatric testing and phlebotomy. Peripheral blood mononuclear cells were quantified for T and B cell subsets using flow cytometry, and serum cytokine concentrations were measured using multiplex immunoassay.

Results: We detected reduced relative numbers of helper T cells and reduced activation of B cells in DLB compared with AD. Additionally, interleukin (IL)-1β was detected more frequently in DLB and the serum concentration of IL-6 was increased compared with controls.

Conclusions: Peripheral inflammation is altered in DLB compared with AD, with T cell subset analysis supporting a possible shift towards senescence of the adaptive immune system in DLB. Furthermore, there is a proinflammatory signature of serum cytokines in DLB. Identification of this unique peripheral immunophenotype in DLB could guide development of an immune-based biomarker and direct future work exploring potential immune modulation as a novel treatment.

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Peripheral inflammation in DLB and AD - Accepted Manuscript
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Accepted/In Press date: 30 July 2020
e-pub ahead of print date: 23 September 2020
Published date: November 2020
Additional Information: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.

Identifiers

Local EPrints ID: 443115
URI: http://eprints.soton.ac.uk/id/eprint/443115
ISSN: 0022-3050
PURE UUID: 1983d497-1314-4fac-9eb5-a6ba7368c1a2
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 Jessica Teeling: ORCID iD orcid.org/0000-0003-4004-7391
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912

Catalogue record

Date deposited: 11 Aug 2020 16:31
Last modified: 26 Nov 2021 07:17

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Contributors

Author: Jay Amin ORCID iD
Author: Delphine Boche ORCID iD
Author: Zoe Clough
Author: Jessica Teeling ORCID iD
Author: Yifang Gao
Author: Lindsey Chudley
Author: Laurie Lau
Author: Florence Smith
Author: Scott Harris
Author: Clive Holmes ORCID iD

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