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

Álvaro Gragera Martinez^1*Cristina Borrachero Garro²Francisco Muñoz Beamud²Ana Manovel Sánchez²Andrés González Macías²Mariano Pizarro Sánchez²Amelia Jiménez Heffernan²Ana Serrano Mira²Beatriz Macías Dominguez²Sandra Garcia Garrido²

• ¹Hospital Juan Ramón Jiménez, Huelva, Spain
• ²Hospital Universitario Juan Ramon Jimenez, Huelva, Spain

Background: Neurofilament 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. Methods: Serum NfL were measured using ELISA and the single-molecule array (SIMoA) technique. Disease severity was assessed with a polyneuropathy disability score (PND). Results: Seventy-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%). Conclusions: Serum 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.