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

Daniela Rossi, Paolo Volanti, Liliana Brambilla, Tiziana Colletti, Rossella Spataro, Vincenzo La Bella

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)510-521
Number of pages12
JournalJournal of Neurology
Volume265
Issue number3
DOIs
Publication statusPublished - Mar 2018

Keywords

  • Aged
  • Amyotrophic Lateral Sclerosis/cerebrospinal fluid
  • Area Under Curve
  • Biomarkers/cerebrospinal fluid
  • Diagnosis, Differential
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation/cerebrospinal fluid
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neurofilament Proteins/cerebrospinal fluid
  • Oligoclonal Bands/cerebrospinal fluid
  • Phosphorylation
  • Prognosis
  • ROC Curve

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