AUTHOR=Gragera-Martínez Álvaro , Borrachero Garro Cristina , Muñoz Beamud Francisco , Manovel Sánchez Ana , González Macías Andrés , Pizarro Sánchez Mariano , Jiménez Heffernan Amelia , Serrano Mira Ana , Macías Dominguez Beatriz , Garcia Garrido Sandra 

TITLE=Clinical utility of neurofilament light chain as a biomarker for disease onset and progression in hereditary transthyretin amyloidosis

JOURNAL=Frontiers in Neurology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2025.1660344

DOI=10.3389/fneur.2025.1660344

ISSN=1664-2295

ABSTRACT=BackgroundNeurofilament light chain levels (NfL) have emerged as a biomarker for early diagnosis and follow-up of hereditary transthyretin variant amyloidosis (ATTRv). We evaluated the most accurate technique for NfL quantifying in ATTRv healthy carriers and symptomatic patients in real-life practice, and assessed whether NfL may represent a reliable biomarker of disease onset and progression.MethodsSerum NfL were measured using ELISA and the single-molecule array (SIMoA) technique. Disease severity was assessed with a polyneuropathy disability score (PND).ResultsSeventy-five subjects with pathogenic transthyretin variant (40 ATTRv healthy carriers and 35 ATTRv patients) were enrolled. We observed a significant correlation between ELISA and SIMoA assay (Pearson’s R2-value = 0.9899). Compared to healthy carriers, patients with symptomatic ATTRv had statistically higher serum NfL levels (p < 0.001). We propose a NfL cut-off of 7.9 pg./mL to distinguish between healthy carriers and ATTRv patients with high diagnostic accuracy (AUC = 0.847; p < 0.001; sensitivity = 90.0%; specificity = 55.0%), whereas the NfL threshold of 18.4 pg./mL discriminated the transition from patients with PND I to PND ≥ II (AUC = 0.695; p < 0.001; sensitivity = 67.0%, specificity = 86%).ConclusionSerum NfL can be accurately quantified using both ELISA and SIMoA array, and it seems to be a reliable biomarker to detect the transition from presymptomatic to symptomatic disease onset and to monitor disease progression.