Population-based Evidence for Using Serum Neurofilaments as Individual Diagnostic and Prognostic Biomarkers in Amyotrophic Lateral Sclerosis

Abstract

Neurofilaments are biomarkers for neuroaxonal damage and are being evaluated in Amyotrophic Lateral Sclerosis (ALS) to support diagnosis, estimate prognosis, and monitor treatment effects. This study presents data on serum neurofilament levels in ALS on a population level to improve their application as individual diagnostic and prognostic biomarkers. We measured neurofilament light (NfL) and phosphorylated heavy chain (pNfH) levels in a large cohort of patients with ALS and controls from the epidemiological ALS registry Swabia. We observed that serum NfL was superior to pNfH. Using NfL Z-Scores instead of raw data and incorporating ALS-independent and ALS-specific influencing factors improved the diagnostic and prognostic ability. The high predictive value and individual longitudinal validity of serum NfL indicate its utility as an individual surrogate marker for survival and disease progression. Combiningepidemiological data and biomarker research in population-based Z-Scores might be a conceptual model of interest for other neurodegenerative diseases.