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Inflammation in Dementia with Lewy bodies and Alzheimer’s disease

Inflammation in Dementia with Lewy bodies and Alzheimer’s disease
Inflammation in Dementia with Lewy bodies and Alzheimer’s disease
Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia. However, the aetiology of DLB remains poorly understood in comparison with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Current evidence supports that neuroinflammation, with involvement of the peripheral immune system, occurs in both AD and PD. Genetic studies in particular support an aetiological role for inflammation in AD rather than it being merely a consequence of neurodegeneration.

Despite extensive research into the role of inflammation in AD and PD, there have been a paucity of studies in DLB. I hypothesised that DLB would show a specific cerebral and systemic inflammatory profile. In order to investigate this hypothesis, two studies were performed. A cross-sectional clinical study investigated peripheral inflammation in DLB, AD and controls using flow cytometry and multiplex immunoassay, and post-mortem human brain tissue work examined microglial immunophenotype in DLB, AD and controls using immunohistochemistry.

The clinical study revealed increased serum concentrations of two proinflammatory cytokines (IL1β and IL6) in DLB compared with controls. In addition, flow cytometry showed a decline in cell populations associated with adaptive immunity (helper T cells and activated B cells) in DLB compared to AD. These data demonstrate senescence of the adaptive immune system in DLB compared with AD, possibly driving a chronic inflammatory state.

The post-mortem work confirmed increased cerebral protein deposition in DLB and AD, but the two diseases showed markedly different microglial phenotypes. AD was characterised by a strong phagocytic microglial phenotype, but in DLB there was no evidence of increased activation of any phenotype. These findings may be associated with the different profiles of the peripheral adaptive immune system, with AD characterised by increased antibody-mediated microglial activation compared with DLB.

The two studies undertaken as part of this project appear to show that the immunophenotype of DLB is distinct from that of AD, with cerebral inflammation not a primary feature of DLB as it is in AD. This has therapeutic implications in that the use of anti-inflammatory therapy may not indicated in DLB. Furthermore, identification of a unique peripheral immune profile in DLB warrants further exploration in order to develop a blood-based immune biomarker that could differentiate these two diseases.
University of Southampton
Amin, Jay
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Amin, Jay
b91805fc-c9fe-4504-94c6-49189e512458
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96

Amin, Jay (2019) Inflammation in Dementia with Lewy bodies and Alzheimer’s disease. University of Southampton, Doctoral Thesis, 264pp.

Record type: Thesis (Doctoral)

Abstract

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia. However, the aetiology of DLB remains poorly understood in comparison with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Current evidence supports that neuroinflammation, with involvement of the peripheral immune system, occurs in both AD and PD. Genetic studies in particular support an aetiological role for inflammation in AD rather than it being merely a consequence of neurodegeneration.

Despite extensive research into the role of inflammation in AD and PD, there have been a paucity of studies in DLB. I hypothesised that DLB would show a specific cerebral and systemic inflammatory profile. In order to investigate this hypothesis, two studies were performed. A cross-sectional clinical study investigated peripheral inflammation in DLB, AD and controls using flow cytometry and multiplex immunoassay, and post-mortem human brain tissue work examined microglial immunophenotype in DLB, AD and controls using immunohistochemistry.

The clinical study revealed increased serum concentrations of two proinflammatory cytokines (IL1β and IL6) in DLB compared with controls. In addition, flow cytometry showed a decline in cell populations associated with adaptive immunity (helper T cells and activated B cells) in DLB compared to AD. These data demonstrate senescence of the adaptive immune system in DLB compared with AD, possibly driving a chronic inflammatory state.

The post-mortem work confirmed increased cerebral protein deposition in DLB and AD, but the two diseases showed markedly different microglial phenotypes. AD was characterised by a strong phagocytic microglial phenotype, but in DLB there was no evidence of increased activation of any phenotype. These findings may be associated with the different profiles of the peripheral adaptive immune system, with AD characterised by increased antibody-mediated microglial activation compared with DLB.

The two studies undertaken as part of this project appear to show that the immunophenotype of DLB is distinct from that of AD, with cerebral inflammation not a primary feature of DLB as it is in AD. This has therapeutic implications in that the use of anti-inflammatory therapy may not indicated in DLB. Furthermore, identification of a unique peripheral immune profile in DLB warrants further exploration in order to develop a blood-based immune biomarker that could differentiate these two diseases.

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Published date: February 2019

Identifiers

Local EPrints ID: 436545
URI: http://eprints.soton.ac.uk/id/eprint/436545
PURE UUID: aff2ca18-5f43-4958-a404-debb7e35af02
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

Catalogue record

Date deposited: 12 Dec 2019 17:30
Last modified: 16 Jul 2020 04:01

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Contributors

Author: Jay Amin ORCID iD
Thesis advisor: Delphine Boche ORCID iD
Thesis advisor: Clive Holmes ORCID iD

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