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Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases

BACKGROUND: Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investi...

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Autores principales: Braun, Madelene, Boström, Gustaf, Ingelsson, Martin, Kilander, Lena, Löwenmark, Malin, Nyholm, Dag, Burman, Joachim, Niemelä, Valter, Freyhult, Eva, Kultima, Kim, Virhammar, Johan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571396/
https://www.ncbi.nlm.nih.gov/pubmed/37833765
http://dx.doi.org/10.1186/s12987-023-00472-x
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author Braun, Madelene
Boström, Gustaf
Ingelsson, Martin
Kilander, Lena
Löwenmark, Malin
Nyholm, Dag
Burman, Joachim
Niemelä, Valter
Freyhult, Eva
Kultima, Kim
Virhammar, Johan
author_facet Braun, Madelene
Boström, Gustaf
Ingelsson, Martin
Kilander, Lena
Löwenmark, Malin
Nyholm, Dag
Burman, Joachim
Niemelä, Valter
Freyhult, Eva
Kultima, Kim
Virhammar, Johan
author_sort Braun, Madelene
collection PubMed
description BACKGROUND: Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investigate whether levels of inflammatory proteins in CSF are different in iNPH compared to healthy controls and patients with selected neurodegenerative disorders, and whether any of these markers can aid in the differential diagnosis of iNPH. METHODS: Lumbar CSF was collected from 172 patients from a single center and represented iNPH (n = 74), Alzheimer’s disease (AD) (n = 21), mild cognitive impairment (MCI) due to AD (n = 21), stable MCI (n = 22), frontotemporal dementia (n = 13), and healthy controls (HC) (n = 21). Levels of 92 inflammatory proteins were analyzed using a proximity extension assay. As a first step, differences between iNPH and HC were investigated, and proteins that differed between iNPH and HC were then compared with those from the other groups. The linear regressions were adjusted for age, sex, and plate number. RESULTS: Three proteins showed higher (MCP-1, p = 0.0013; CCL4, p = 0.0008; CCL11, p = 0.0022) and one lower (PD-L1, p = 0.0051) levels in patients with iNPH compared to HC. MCP-1 was then found to be higher in iNPH than in all other groups. CCL4 was higher in iNPH than in all other groups, except in MCI due to AD. PD-L1 was lower in iNPH compared to all other groups, except in stable MCI. Levels of CCL11 did not differ between iNPH and the differential diagnoses. In a model based on the four proteins mentioned above, the mean area under the receiver operating characteristic curve used to discriminate between iNPH and the other disorders was 0.91. CONCLUSIONS: The inflammatory cytokines MCP-1 and CCL4 are present at higher—and PD-L1 at lower—levels in iNPH than in the other investigated diagnoses. These three selected cytokines may have diagnostic potential in the work-up of patients with iNPH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12987-023-00472-x.
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spelling pubmed-105713962023-10-14 Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases Braun, Madelene Boström, Gustaf Ingelsson, Martin Kilander, Lena Löwenmark, Malin Nyholm, Dag Burman, Joachim Niemelä, Valter Freyhult, Eva Kultima, Kim Virhammar, Johan Fluids Barriers CNS Research BACKGROUND: Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investigate whether levels of inflammatory proteins in CSF are different in iNPH compared to healthy controls and patients with selected neurodegenerative disorders, and whether any of these markers can aid in the differential diagnosis of iNPH. METHODS: Lumbar CSF was collected from 172 patients from a single center and represented iNPH (n = 74), Alzheimer’s disease (AD) (n = 21), mild cognitive impairment (MCI) due to AD (n = 21), stable MCI (n = 22), frontotemporal dementia (n = 13), and healthy controls (HC) (n = 21). Levels of 92 inflammatory proteins were analyzed using a proximity extension assay. As a first step, differences between iNPH and HC were investigated, and proteins that differed between iNPH and HC were then compared with those from the other groups. The linear regressions were adjusted for age, sex, and plate number. RESULTS: Three proteins showed higher (MCP-1, p = 0.0013; CCL4, p = 0.0008; CCL11, p = 0.0022) and one lower (PD-L1, p = 0.0051) levels in patients with iNPH compared to HC. MCP-1 was then found to be higher in iNPH than in all other groups. CCL4 was higher in iNPH than in all other groups, except in MCI due to AD. PD-L1 was lower in iNPH compared to all other groups, except in stable MCI. Levels of CCL11 did not differ between iNPH and the differential diagnoses. In a model based on the four proteins mentioned above, the mean area under the receiver operating characteristic curve used to discriminate between iNPH and the other disorders was 0.91. CONCLUSIONS: The inflammatory cytokines MCP-1 and CCL4 are present at higher—and PD-L1 at lower—levels in iNPH than in the other investigated diagnoses. These three selected cytokines may have diagnostic potential in the work-up of patients with iNPH. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12987-023-00472-x. BioMed Central 2023-10-13 /pmc/articles/PMC10571396/ /pubmed/37833765 http://dx.doi.org/10.1186/s12987-023-00472-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Braun, Madelene
Boström, Gustaf
Ingelsson, Martin
Kilander, Lena
Löwenmark, Malin
Nyholm, Dag
Burman, Joachim
Niemelä, Valter
Freyhult, Eva
Kultima, Kim
Virhammar, Johan
Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
title Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
title_full Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
title_fullStr Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
title_full_unstemmed Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
title_short Levels of inflammatory cytokines MCP-1, CCL4, and PD-L1 in CSF differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
title_sort levels of inflammatory cytokines mcp-1, ccl4, and pd-l1 in csf differentiate idiopathic normal pressure hydrocephalus from neurodegenerative diseases
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10571396/
https://www.ncbi.nlm.nih.gov/pubmed/37833765
http://dx.doi.org/10.1186/s12987-023-00472-x
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