Multicenter validation of CSF neurofilaments as diagnostic biomarkers for ALS

Amyotroph Lateral Scler Frontotemporal Degener. 2016 Jul-Aug;17(5-6):404-13. doi: 10.3109/21678421.2016.1167913. Epub 2016 Apr 11.

Abstract

Objective: Neurofilaments are leading neurochemical biomarkers for amyotrophic lateral sclerosis (ALS). Here, we investigated the effect of preanalytical factors on neurofilament concentrations in cerebrospinal fluid (CSF) in a "reverse" round-robin with 15 centers across Europe/U.S.

Methods: Samples from ALS and control patients (5/5 each center, n = 150) were analyzed for phosphorylated neurofilament heavy chain (pNfH) and neurofilament light chain (NfL) at two laboratories.

Results: CSF pNfH was increased (p < 0.05) in ALS in 10 out of 15 centers and NfL in 5 out of 12 centers. The coefficient of variation (CV%) of pNfH measurements between laboratories was 18.7 ± 19.1%. We calculated a diagnostic cut-off of >568.5 pg/mL for pNfH (sensitivity 78.7%, specificity 93.3%) and >1,431pg/mL for NfL (sensitivity 79.0%, specificity 86.4%).

Conclusion: Values in ALS patients are already comparable between most centers, supporting eventual implementation into clinical routine. However, continuous quality control programs will be necessary for inclusion in the diagnostic work-up.

Keywords: Cerebrospinal fluid; amyotrophic lateral sclerosis; biomarker; neurofilament; round robin.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid*
  • Enzyme-Linked Immunosorbent Assay
  • Europe
  • Female
  • Humans
  • Intermediate Filaments / metabolism*
  • Male
  • Middle Aged
  • Phosphorylation
  • Reproducibility of Results
  • Statistics, Nonparametric
  • United States

Substances

  • Biomarkers