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Journal of Neurology

, Volume 265, Issue 3, pp 510–521 | Cite as

CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis

  • Daniela Rossi
  • Paolo Volanti
  • Liliana Brambilla
  • Tiziana Colletti
  • Rossella Spataro
  • Vincenzo La BellaEmail author
Original Communication

Abstract

Elevated cerebrospinal fluid (CSF), Neurofilament Light (NF-L) and phosphorylated Heavy (pNF-H) chain levels have been found in Amyotrophic Lateral Sclerosis (ALS), with studies reporting a correlation of both neurofilaments (NFs) with the disease progression. Here, we measured NF-L and pNF-H concentrations in the CSF of ALS patients from a single tertiary Center and investigated their relationship with disease-related variables. A total of 190 ALS patients (Bulbar, 29.9%; Spinal, 70.1%; M/F = 1.53) and 130 controls with mixed neurological diseases were recruited. Demographic and clinical variables were recorded, and ΔFS was used to rate the disease progression. Controls were divided into two cohorts: (1) patients with non-inflammatory neurological diseases (CTL-1); (2) patients with acute/subacute inflammatory diseases and tumors, expected to lead to significant axonal and tissue damage (CTL-2). For each patient and control, CSF was taken at the time of the diagnostic work-up and stored following the published guidelines. CSF NF-L and pNF-H were assayed with commercially available ELISA-based methods. Standard curves (from independent ELISA kits) were highly reproducible for both NFs, with a coefficient of variation < 20%. We found that CSF NF-L and pNF-H levels in ALS were significantly increased when compared to CTL-1 (NF-L: ALS, 4.7 ng/ml vs CTL-1, 0.61 ng/ml, p < 0.001; pNF-H: ALS, 1.7 ng/ml vs CTL-1, 0.03 ng/ml, p < 0.0001), but not to CTL-2. Analysis of different clinical and prognostic variables disclosed meaningful correlations with both NF-L and pNF-H levels. Our results, from a relatively large ALS cohort, confirm that CSF NF-L and pNF-H represent valuable diagnostic and prognostic biomarkers in ALS.

Keywords

ALS Neurofilaments NF-L pNF-H Disease progression CSF 

Notes

Acknowledgements

This work was supported by funds from the Italian Ministry of Health for the Ricerca Corrente to IRCCS Istituti Clinici Scientifici Maugeri SpA SB.

Compliance with ethical standards

Conflicts of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest related to the Ms JOON-D-17-01506.

Supplementary material

415_2017_8730_MOESM1_ESM.docx (132 kb)
Supplementary material 1 (DOCX 132 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory for Research on Neurodegenerative DisordersICS MaugeriPaviaItaly
  2. 2.ALS Center and Neurorehabilitation UnitICS MaugeriMistrettaItaly
  3. 3.Department of Experimental BioMedicine and Clinical Neurosciences, ALS Clinical Research CenterUniversity of PalermoPalermoItaly

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