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Inflammation in Dementia with Lewy bodies

Inflammation in Dementia with Lewy bodies
Inflammation in Dementia with Lewy bodies
Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). There is mounting evidence supporting a role for inflammation in the aetiology of AD, with the innate immune cells of the brain, microglia, being key players. In contrast, our understanding of the role of inflammation in DLB is much less well developed. We hypothesise that inflammatory processes will show a profile specific to DLB and will be significantly associated with the neuropathological and clinical features of the disease. Methods: a) Neuropathology study: Post-mortem human brain sections from the middle temporal gyrus of 69 cases (38 DLB, 31 age-matched controls) were immunostained for markers of neuropathology (a-synuclein, amyloid-b, p-tau), microglial activation (Iba1, HLA-DR, CD68) and FcgRs (CD64, CD32a, CD32b and CD16). Quantification was performed to obtain protein load (%) using Image J. b) Clinical biomarker study: 90 participants (30 DLB, 30 AD, 30 controls) are entering an observational, cross-sectional study. ELISA and flow cytometry are being used to investigate blood markers of systemic inflammation. Results: a) In the DLB brain there was significantly higher a-synuclein and amyloid-b (p=0.039) protein load, with a trend for higher p-tau (p=0.052) load, compared to controls. No significant difference was found in the load of microglial activation markers Iba1 (p=0.307), HLA-DR (p=0.832) or CD68 (p=0.064). However, FcgR markers did show significantly decreased CD32a (p=0.043) and increased CD16 load (p=0.027) in DLB compared to controls, but there was no difference in CD64 (p=0.582) or CD32b load (p=0.976). No significant correlations were found between any neuropathological and any inflammatory marker in either cohort. b) Clinical study is due to complete in 2017. Conclusions: Despite the confirmation of increased neuropathology in the DLB brain, this did not appear to affect the expression of microglia, as previously seen in AD. However, the FcgR profile does appear to be modified in DLB. Ongoing work aims to investigate systemic inflammation in the clinical study, with the potential for identification of a unique inflammatory signature in DLB.
1552-5260
P594-P595
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Williams, Tony
98ce6bb8-51ae-4fc8-abf1-2f83fc24dc08
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Dorey, Robert
8d4b042f-1659-4e76-99c2-23cde78ca4f5
Williams, Daisy
bca59d42-e48b-4073-9d68-79f0746def91
Tommasino, Emmanuele
842485c9-3bb2-4872-94a2-627b034ac5d5
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61
Amin, Jay
692a8880-70ff-4b64-a7e9-7d0d53449a30
Williams, Tony
98ce6bb8-51ae-4fc8-abf1-2f83fc24dc08
Teeling, Jessica
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Dorey, Robert
8d4b042f-1659-4e76-99c2-23cde78ca4f5
Williams, Daisy
bca59d42-e48b-4073-9d68-79f0746def91
Tommasino, Emmanuele
842485c9-3bb2-4872-94a2-627b034ac5d5
Holmes, Clive
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Boche, Delphine
bdcca10e-6302-4dd0-919f-67218f7e0d61

Amin, Jay, Williams, Tony, Teeling, Jessica, Dorey, Robert, Williams, Daisy, Tommasino, Emmanuele, Holmes, Clive and Boche, Delphine (2017) Inflammation in Dementia with Lewy bodies. Alzheimer's & Dementia, 13 (7, Supplement), P594-P595. (doi:10.1016/j.jalz.2017.07.232).

Record type: Meeting abstract

Abstract

Background: Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer's disease (AD). There is mounting evidence supporting a role for inflammation in the aetiology of AD, with the innate immune cells of the brain, microglia, being key players. In contrast, our understanding of the role of inflammation in DLB is much less well developed. We hypothesise that inflammatory processes will show a profile specific to DLB and will be significantly associated with the neuropathological and clinical features of the disease. Methods: a) Neuropathology study: Post-mortem human brain sections from the middle temporal gyrus of 69 cases (38 DLB, 31 age-matched controls) were immunostained for markers of neuropathology (a-synuclein, amyloid-b, p-tau), microglial activation (Iba1, HLA-DR, CD68) and FcgRs (CD64, CD32a, CD32b and CD16). Quantification was performed to obtain protein load (%) using Image J. b) Clinical biomarker study: 90 participants (30 DLB, 30 AD, 30 controls) are entering an observational, cross-sectional study. ELISA and flow cytometry are being used to investigate blood markers of systemic inflammation. Results: a) In the DLB brain there was significantly higher a-synuclein and amyloid-b (p=0.039) protein load, with a trend for higher p-tau (p=0.052) load, compared to controls. No significant difference was found in the load of microglial activation markers Iba1 (p=0.307), HLA-DR (p=0.832) or CD68 (p=0.064). However, FcgR markers did show significantly decreased CD32a (p=0.043) and increased CD16 load (p=0.027) in DLB compared to controls, but there was no difference in CD64 (p=0.582) or CD32b load (p=0.976). No significant correlations were found between any neuropathological and any inflammatory marker in either cohort. b) Clinical study is due to complete in 2017. Conclusions: Despite the confirmation of increased neuropathology in the DLB brain, this did not appear to affect the expression of microglia, as previously seen in AD. However, the FcgR profile does appear to be modified in DLB. Ongoing work aims to investigate systemic inflammation in the clinical study, with the potential for identification of a unique inflammatory signature in DLB.

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Published date: July 2017

Identifiers

Local EPrints ID: 443612
URI: http://eprints.soton.ac.uk/id/eprint/443612
ISSN: 1552-5260
PURE UUID: 3549a39f-5408-45c3-9ba6-87ade5a0ae0c
ORCID for Jay Amin: ORCID iD orcid.org/0000-0003-3792-0428
ORCID for Jessica Teeling: ORCID iD orcid.org/0000-0003-4004-7391
ORCID for Clive Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for Delphine Boche: ORCID iD orcid.org/0000-0002-5884-130X

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Date deposited: 04 Sep 2020 16:32
Last modified: 26 Nov 2021 03:03

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Contributors

Author: Jay Amin ORCID iD
Author: Tony Williams
Author: Jessica Teeling ORCID iD
Author: Robert Dorey
Author: Daisy Williams
Author: Emmanuele Tommasino
Author: Clive Holmes ORCID iD
Author: Delphine Boche ORCID iD

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