Phosphorylated neurofilament heavy chain levels in paired plasma and CSF of amyotrophic lateral sclerosis

Abstract

Background and objective: Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by degeneration of both upper and lower motor neurons. In this study, we aimed to measure both plasma and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNF-H) levels in patients with ALS, and determine if there is a correlation. We also evaluated plasma and CSF pNF-H levels to investigate if this biomarker could predict the time to generalization (TTG) in ALS better.

Methods: Paired plasma and CSF pNF-H levels of patients with ALS (n=51), multiple system atrophy (n=12) and controls (n=30) were measured by monoclonal sandwich ELISA. TTG, which also indicates the time of symptoms spreading from spinal or bulbar localization to both, was evaluated in all ALS patients.

Results: We found a strong correlation between plasma and CSF pNF-H levels within individual patients (r=0.712, p<0.001). The mean TTG in ALS patients was 22.9months (range 1-84months), and there was an inverse correlation between plasma (r=-0.661; p<0.001)/CSF (r=-0.869; p<0.001) pNF-H levels and TTG.

Conclusion: The correlation of plasma and CSF pNF-H levels would bring insight into the pathogenesis of ALS. TTG might play an important role in the future study of ALS, as an early indicator of survival.

Keywords: Amyotrophic lateral sclerosis; Biomarker; CSF; Neurofilament; Plasma; Time to generalization.