Plasma neurofilament medium chain: a cross-sectional study to evaluate its value as a disease-progression biomarker of amyotrophic lateral sclerosis

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal progressive neurodegenerative disease where the majority of patients invariably die within 3 years from the onset of symptoms. To date there are no validated prognostic biomarkers for ALS notwithstanding the continuous research in the field and promising results from the study of neurofilament light and heavy chain (Lu C-H, Macdonald-Wallis C, Gray E, et al., Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis, Neurology 2015; 84(22):2247-57; Lu C-H, Petzold A, Topping J, et al., Plasma neurofilament heavy chain levels and disease progression in amyotrophic lateral sclerosis: insights from a longitudinal study; J Neurol Neurosurg Psychiatry 2015; 86(5):565-73). Objective: Neurofilament medium chain (NfM) is the intermediate length isoform of neurofilament proteins, the main neuronal structural proteins. In spite of its extensive presence in CNS and PNS, neurofilament medium has never been tested in this pathology affecting upper and lower motoneurons. A recent study has shown NfM is one of the proteins with the most significant ALS disease-associated differences in plasma-profiling via affinity proteomics (Häggmark A, Mikus M, Mohsenchian A, et al.; Plasma profiling reveals three proteins associated to amyotrophic lateral sclerosis, Ann Clin Transl Neurol 2014;1(8):544-53). We tested for the first time plasma levels of NfM with a commercially-available ELISA kit (Cloud-Clone Corp, SEB326Hu) in a cross-sectional cohort of, age-matched, 81 ALS patients and 79 healthy controls. Results: We did not observe any significant difference of plasma NfM levels between patients and controls. There was no differential trends in ALS patients stratified according to clinical progressions, nor significant correlations. Discussion: Considering the great heterogeneity of ALS and relatively small case number as well as short observation period in this study, further validation in a larger, longitudinal cohort is necessary to determine whether plasma NfM may be a disease progression marker of ALS.