Neurofilament light: A candidate biomarker of presymptomatic amyotrophic lateral sclerosis and phenoconversion

Michael Benatar, Joanne Wuu, Peter M. Andersen, Vittoria Lombardi, Andrea Malaspina

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Objective: To evaluate neurofilament light (NfL) as a biomarker of the presymptomatic phase of amyotrophic lateral sclerosis (ALS). Methods: The study population includes 84 individuals at risk for developing ALS, 34 controls, 17 ALS patients, and 10 phenoconverters (at-risk individuals observed both before and after the emergence of clinically manifest disease). At-risk individuals are enrolled through Pre-Symptomatic Familial ALS (Pre-fALS), a longitudinal natural history and biomarker study of individuals who are carriers of any ALS-associated gene mutation (in SOD1, C9orf72, TARDBP, FUS, VCP, etc), but who, at the time of enrollment, demonstrated no clinical symptoms or signs (including electromyographic evidence) of manifest disease. NfL in serum and cerebrospinal fluid (CSF) were quantified using an electrochemiluminescence immunoassay. Results: Serum and CSF NfL are substantially higher in ALS patients compared to controls and at-risk individuals and remain relatively stable over time. Among phenoconverters, however, NfL levels were elevated (ie, above the range observed in controls) as far back as ∼12 months preceding the emergence of the earliest clinical symptoms or signs of disease. Interpretation: Serum (and CSF) NfL are informative biomarkers of presymptomatic ALS, providing a new tool to quantify presymptomatic disease progression and to potentially predict the timing of clinical phenoconversion. As such, quantification of NfL may aid the design and implementation of early therapeutic intervention for affected individuals and/or disease prevention trials for individuals at short-term risk of developing ALS. Ann Neurol 2018 Ann Neurol 2018;83:130–139.

Original languageEnglish (US)
Pages (from-to)130-139
Number of pages10
JournalAnnals of neurology
Issue number1
StatePublished - Jul 2018

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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