Impact of age on neurofilament light chain in Friedreich ataxia: a 1-year longitudinal study

Friedreich's ataxia (FRDA) is a recessive inherited ataxia caused by intronic GAA repeat expansions in FXN gene. The repeat length is the major determinant of age at onset, usually occurring in adolescence. Clinical manifestations include progressive gait and limb ataxia, sensory loss, cardiomyopathy, and scoliosis. Neurofilament light chain protein (NfL) has been recently studied as a potential plasma biomarker for the disease. We performed a longitudinal study in 62 patients with FRDA, including 12 children (age 12-17 years) and 50 adult patients (age 18-45). The characteristics of our patient cohort largely matched those of a population mostly recruited in therapeutical clinical trials, with a mean age of 25.1 ± 8.5 years, age at onset 13.1 ± 4.8 years, and disease duration 12 ± 7 years. We found higher NfL levels in children in comparison with adult patients. Plasma concentrations remained stable at 1-year follow-up. We observed a significantly inverse correlation between plasma NfL levels and patient ages, while no correlations were found with other clinical or genetic variables. Our study confirms the typical NfL profile in FRDA patients. Our data further support the role of NfL as early indicator of axonal damage and as potential pharmacodynamic biomarker of therapeutical response especially valuable in pediatric populations.