Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

Federico Verde, Petra Steinacker, Jochen H Weishaupt, Jan Kassubek, Patrick Oeckl, Steffen Halbgebauer, Hayrettin Tumani, Christine A F von Arnim, Johannes Dorst, Emily Feneberg, Benjamin Mayer, Hans-Peter Müller, Martin Gorges, Angela Rosenbohm, Alexander E Volk, Vincenzo Silani, Albert C Ludolph, Markus Otto

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalJournal of neurology, neurosurgery, and psychiatry
Volume90
Issue number2
DOIs
Publication statusPublished - Feb 2019

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Verde, F., Steinacker, P., Weishaupt, J. H., Kassubek, J., Oeckl, P., Halbgebauer, S., Tumani, H., von Arnim, C. A. F., Dorst, J., Feneberg, E., Mayer, B., Müller, H-P., Gorges, M., Rosenbohm, A., Volk, A. E., Silani, V., Ludolph, A. C., & Otto, M. (2019). Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. Journal of neurology, neurosurgery, and psychiatry, 90(2), 157-164. https://doi.org/10.1136/jnnp-2018-318704