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Research paper
Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis
  1. Federico Verde1,2,
  2. Petra Steinacker1,
  3. Jochen H Weishaupt1,
  4. Jan Kassubek1,
  5. Patrick Oeckl1,
  6. Steffen Halbgebauer1,
  7. Hayrettin Tumani1,
  8. Christine A F von Arnim1,
  9. Johannes Dorst1,
  10. Emily Feneberg1,3,
  11. Benjamin Mayer4,
  12. Hans-Peter Müller1,
  13. Martin Gorges1,
  14. Angela Rosenbohm1,
  15. Alexander E Volk5,
  16. Vincenzo Silani2,
  17. Albert C Ludolph1,
  18. Markus Otto1
  1. 1 Department of Neurology, University of Ulm, Ulm, Germany
  2. 2 Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, and Department of Pathophysiology and Transplantation, ‘Dino Ferrari’ Center, Università degli Studi di Milano, Milan, Italy
  3. 3 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  4. 4 Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
  5. 5 Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  1. Correspondence to Professor Markus Otto, Department of Neurology, University of Ulm, Ulm 89081, Germany; markus.otto{at}uni-ulm.de

Abstract

Objective To determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).

Methods This single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer’s disease, 19 with Parkinson’s disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.

Results Serum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.

Conclusions Serum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.

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Footnotes

  • Contributor Study conception and design: MO, ACL, FV. Acquisition and analysis of data: FV, PS, JHW, JK, SH, JD, BM, HPM, MG, AEV, ACL, MO. Writing of the manuscript: FV, PS, MO. Critical revision of the manuscript: FV, PS, JHW, JK, PO, SH, HT, CAFvA, JD, EF, BM, HPM, MG, AR, AEV, VS, ACL, MO.

  • Funding The study was supported by grants from the German Federal Ministry of Education and Research (project FTDc 01GI1007A, MND-Net 01GI0704), the EU Joint Programme–Neurodegenerative Diseases network PreFrontAls (01ED1512), the German Research Foundation (VO 2028/1-1), the Foundation of the State of Baden-Wuerttemberg, the Thierry Latran Foundation, the ALS Association, the Virtual Helmholtz Institute ‘RNA Dysmetabolism in FTD and ALS’ and Boehringer Ingelheim Ulm University BioCenter.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Ethics Committee of Ulm University (proposal number 20/10, year 2010).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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