Peripheral and cerebrospinal fluid inflammatory markers in sporadic amyotrophic lateral sclerosis an exploratory cross-sectional association study.
- 1Department of Neurology, Pomeranian Medical University, Unii Lubelskiej 1 Str 71-252 Szczecin, Szczecin, Poland. [email protected].
- 2Department of General Pathology, Pomeranian Medical University, Szczecin, Poland.
- 3Department of Neurology, Pomeranian Medical University, Unii Lubelskiej 1 Str 71-252 Szczecin, Szczecin, Poland.
Abstract
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with an ambiguous etiology, whose onset may be linked to innate immune system activation outside the central nervous system (CNS). We investigated the association between peripheral blood and CNS inflammatory parameters in 45 sporadic ALS patients compared to 30 controls, analyzing peripheral blood tests (C-reactive protein [CRP], blood count, fibrinogen) and cerebrospinal fluid (CSF) immunological measures (Tumor Necrosis Factor alpha [TNF-α], TNF receptor type 1 [TNFR-1], CRP) alongside clinical characteristics. Results revealed significantly higher concentrations of TNFR-1 in the CSF of ALS patients compared to the control group (1,029.5 ± 176.0 vs. 846.1 ± 167.5 pg/ml; p < 0.0001). This difference remained significant in multivariable logistic regression adjusting for age and sex (OR 1.82 per 100 pg/ml increment, 95% CI 1.26-2.63; p = 0.0015). In an exploratory ROC analysis, CSF TNFR-1 discriminated patients from controls with an AUC of 0.78 (95% CI 0.67-0.88). TNFR-1 correlated with age (R = 0.32, p = 0.038), associations with disease severity and a lower concentration in bulbar-onset disease were exploratory and not robustly significant. Plasma and CSF CRP concentrations did not differ significantly between groups, but strongly correlated with each other in both ALS (R = 0.83) and control (R = 0.82) cohorts, indicating a disease-non-specific relationship. CSF TNFR-1 is independently associated with sporadic ALS and warrants further investigation as a candidate disease-associated inflammatory biomarker. Given the limitations, our findings do not prove diagnostic accuracy or causality. Longitudinal studies with disease controls and blood-CSF barrier integrity measures are needed.
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BibTeX
@article{welnickawesolowska2026peripheral,
title = {{Peripheral and cerebrospinal fluid inflammatory markers in sporadic amyotrophic lateral sclerosis an exploratory cross-sectional association study.}},
author = {Agnieszka Wełnicka-Wesołowska and Karolina Łuczkowska and Przemysław Nowacki and Edyta Paczkowska and Agnieszka Meller and Karolina Machowska-Sempruch and Bogusław Machaliński and Monika Gołąb-Janowska},
journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology},
year = {2026},
month = oct,
doi = {10.1007/s10072-026-09480-9},
url = {https://europepmc.org/article/MED/42891860},
note = {CC BY},
}
RIS
TY - JOUR
TI - Peripheral and cerebrospinal fluid inflammatory markers in sporadic amyotrophic lateral sclerosis an exploratory cross-sectional association study.
AU - Agnieszka Wełnicka-Wesołowska
AU - Karolina Łuczkowska
AU - Przemysław Nowacki
AU - Edyta Paczkowska
AU - Agnieszka Meller
AU - Karolina Machowska-Sempruch
AU - Bogusław Machaliński
AU - Monika Gołąb-Janowska
PY - 2026
DA - 2026/10/17
JO - Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
DO - 10.1007/s10072-026-09480-9
UR - https://europepmc.org/article/MED/42891860
AB - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder with an ambiguous etiology, whose onset may be linked to innate immune system activation outside the central nervous system (CNS). We investigated the association between peripheral blood and CNS inflammatory parameters in 45 sporadic ALS patients compared to 30 controls, analyzing peripheral blood tests (C-reactive protein [CRP], blood count, fibrinogen) and cerebrospinal fluid (CSF) immunological measures (Tumor Necrosis Factor alpha [TNF-α], TNF receptor type 1 [TNFR-1], CRP) alongside clinical characteristics. Results revealed significantly higher concentrations of TNFR-1 in the CSF of ALS patients compared to the control group (1,029.5 ± 176.0 vs. 846.1 ± 167.5 pg/ml; p < 0.0001). This difference remained significant in multivariable logistic regression adjusting for age and sex (OR 1.82 per 100 pg/ml increment, 95% CI 1.26-2.63; p = 0.0015). In an exploratory ROC analysis, CSF TNFR-1 discriminated patients from controls with an AUC of 0.78 (95% CI 0.67-0.88). TNFR-1 correlated with age (R = 0.32, p = 0.038), associations with disease severity and a lower concentration in bulbar-onset disease were exploratory and not robustly significant. Plasma and CSF CRP concentrations did not differ significantly between groups, but strongly correlated with each other in both ALS (R = 0.83) and control (R = 0.82) cohorts, indicating a disease-non-specific relationship. CSF TNFR-1 is independently associated with sporadic ALS and warrants further investigation as a candidate disease-associated inflammatory biomarker. Given the limitations, our findings do not prove diagnostic accuracy or causality. Longitudinal studies with disease controls and blood-CSF barrier integrity measures are needed.
SN - 1590-1874
SN - 1590-3478
ER -