Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis

Neurology. 2015 Jun 2;84(22):2247-57. doi: 10.1212/WNL.0000000000001642. Epub 2015 May 1.

Abstract

Objective: To test blood and CSF neurofilament light chain (NfL) levels in relation to disease progression and survival in amyotrophic lateral sclerosis (ALS).

Methods: Using an electrochemiluminescence immunoassay, NfL levels were measured in samples from 2 cohorts of patients with sporadic ALS and healthy controls, recruited in London (ALS/control, plasma: n = 103/42) and Oxford (ALS/control, serum: n = 64/36; paired CSF: n = 38/20). NfL levels in patients were measured at regular intervals for up to 3 years. Change in ALS Functional Rating Scale-Revised score was used to assess disease progression. Survival was evaluated using Cox regression and Kaplan-Meier analysis.

Results: CSF, serum, and plasma NfL discriminated patients with ALS from healthy controls with high sensitivity (97%, 89%, 90%, respectively) and specificity (95%, 75%, 71%, respectively). CSF NfL was highly correlated with serum levels (r = 0.78, p < 0.0001). Blood NfL levels were approximately 4 times as high in patients with ALS compared with controls in both cohorts, and maintained a relatively constant expression during follow-up. Blood NfL levels at recruitment were strong, independent predictors of survival. The highest tertile of blood NfL at baseline had a mortality hazard ratio of 3.91 (95% confidence interval 1.98-7.94, p < 0.001).

Conclusion: Blood-derived NfL level is an easily accessible biomarker with prognostic value in ALS. The individually relatively stable levels longitudinally offer potential for NfL as a pharmacodynamic biomarker in future therapeutic trials.

Classification of evidence: This report provides Class III evidence that the NfL electrochemiluminescence immunoassay accurately distinguishes patients with sporadic ALS from healthy controls.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyotrophic Lateral Sclerosis / blood*
  • Amyotrophic Lateral Sclerosis / cerebrospinal fluid*
  • Amyotrophic Lateral Sclerosis / diagnosis
  • Biomarkers / blood
  • Biomarkers / cerebrospinal fluid
  • Cohort Studies
  • Cross-Sectional Studies
  • Disease Progression*
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neurofilament Proteins / blood*
  • Neurofilament Proteins / cerebrospinal fluid*
  • Prognosis

Substances

  • Biomarkers
  • Neurofilament Proteins
  • neurofilament protein L