Serum neurofilament and measures of lower motor neuron dysfunction in amyotrophic lateral sclerosis

Objective Serum neurofilament light chain (NfL) is an emerging diagnostic and prognostic biomarker in amyotrophic lateral sclerosis (ALS). Ulnar far-field potentials (FFP) have also been proposed as a reliable neurophysiological biomarker in ALS. This study examined the relationship between serum NfL levels and neurophysiological biomarkers of lower motor neuron dysfunction in ALS. Methods This study included 96 ALS participants and 53 participants with ALS-mimicking disorders. All participants underwent serum NfL measurement using a single-molecule array (Simoa) assay, together with peripheral neurophysiological assessment, including ulnar nerve FFP, compound motor action potential (CMAP), near-field potential (NFP), split-hand index (SI), and neurophysiological index (NI). Results FFP amplitude was reduced in ALS (5.0 ± 3.0 mV) compared with non-ALS participants (7.9 ± 3.2 mV; p < 0.001). Similar reductions were observed for NFP and CMAP amplitudes (p < 0.001). Serum NfL was higher in ALS participants (72.5 pg/mL, IQR 46.5–113.5) compared to non-ALS controls (14 pg/mL, IQR 9–19; p < 0.001). Serum NfL showed weak negative correlations with CMAP (ρ = -0.23, p = 0.03) and NFP amplitudes (ρ = −0.28, p = 0.01), but no significant correlation with FFP amplitude, SI or NI. After adjusting for disease duration and functional impairment on multiple linear regression, neither CMAP nor NFP amplitudes independently predicted serum NfL levels. Conclusion Serum NfL is elevated in ALS and weakly associated with CMAP and NFP amplitudes. The absence of a statistically significant correlation with FFP suggests that these biomarkers capture distinct aspects of disease biology. Significance Serum NfL and FFP amplitude may provide complementary diagnostic information in ALS.