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

Ann Neurol. 2018 Jul;84(1):130-139. doi: 10.1002/ana.25276. Epub 2018 Aug 16.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amyotrophic Lateral Sclerosis / blood*
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Amyotrophic Lateral Sclerosis / genetics
  • C9orf72 Protein / genetics
  • Cross-Sectional Studies
  • Disease Progression*
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neurofilament Proteins / blood*
  • Neurofilament Proteins / cerebrospinal fluid*
  • Prodromal Symptoms*
  • Superoxide Dismutase-1 / genetics
  • Young Adult


  • C9orf72 Protein
  • C9orf72 protein, human
  • Neurofilament Proteins
  • SOD1 protein, human
  • neurofilament protein L
  • Superoxide Dismutase-1