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

Fluids and Barriers of the CNS

Research

Eva Freyhult¹  Kim Kultima²  Madelene Braun³  Valter Niemelä³  Joachim Burman³  Johan Virhammar³  Dag Nyholm³  Lena Kilander⁴  Malin Löwenmark⁴  Gustaf Boström⁵  Martin Ingelsson⁶ 

[1] Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden;Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden;Department of Medical Sciences, Neurology, Uppsala University, Uppsala, Sweden;Department of Public Health and Caring Sciences, Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden;Department of Public Health and Caring Sciences, Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden;Centre for Clinical Research, Uppsala University, Västmanland County Hospital, Västerås, Sweden;Department of Public Health and Caring Sciences, Molecular Geriatrics, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden;Krembil Brain Institute, University Health Network, Toronto, Ontario, Canada;Tanz Centre for Research in Neurodegenerative Diseases, Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto, Toronto, Ontario, Canada;

关键词: Normal pressure hydrocephalus;    MCP-1;    CCL4;    PD-L1;    Biomarkers;    Cerebrospinal fluid;    Neuroinflammation;    Proteomics;   

DOI  :  10.1186/s12987-023-00472-x

 received in 2023-07-09, accepted in 2023-10-03,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNeuroinflammatory 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.MethodsLumbar 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.ResultsThree 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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