Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis.

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.

• Authors: Ching-Hua Lu, Corrie Macdonald-Wallis, Elizabeth Gray, Neil Pearce, Axel Petzold, Niklas Norgren, Gavin Giovannoni, Pietro Fratta, Katie Sidle, Mark Fish, Richard Orrell, Robin Howard, Kevin Talbot, Linda Greensmith, Jens Kuhle, Martin R Turner, Andrea Malaspina
• Journal: Neurology (Neurology) Vol. 84 Issue 22 Pg. 2247-57 (Jun 02 2015) ISSN: 1526-632X [Electronic] United States
• PMID: 25934855 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Academy of Neurology.

Chemical References

• Biomarkers
• Neurofilament Proteins
• neurofilament protein L

Topics

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