Biological variation of serum neurofilament light chain

• Published in: Clinical chemistry and laboratory medicine Vol. 60; no. 4; pp. 569 - 575
• Main Authors: Hviid, Claus Vinter Bødker, Madsen, Anne Tranberg, Winther-Larsen, Anne
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 28.03.2022; Walter De Gruyter & Company
• Subjects: Biological variation; biomarker; Biomarkers; Biomarkers - blood; Blood; Chains; Confidence intervals; Diurnal variations; Humans; Intermediate Filaments - metabolism; monitoring; neurofilament proteins; Neurofilament Proteins - blood; Reference Values; Variation; biomarker; monitoring; neurofilament proteins; biological variation
• ISSN: 1434-6621; 1437-4331; 1437-4331
• DOI: 10.1515/cclm-2020-1276

The neurofilament light chain (NfL) has emerged as a versatile biomarker for CNS-diseases and is approaching clinical use. The observed changes in NfL levels are frequently of limited magnitude and in order to make clinical decisions based on NfL measurements, it is essential that biological variation is not confused with clinically relevant changes. The present study was designed to evaluate the biological variation of serum NfL. Apparently healthy individuals (n=33) were submitted to blood draws for three days in a row. On the second day, blood draws were performed every third hour for 12 h. NfL was quantified in serum using the Simoa™ HD-1 platform. The within-subject variation (CV ) and between-subject variation (CV ) were calculated using linear mixed-effects models. The overall median value of NfL was 6.3 pg/mL (range 2.1-19.1). The CV was 3.1% and the CV was 35.6%. An increase in two serial measurements had to exceed 24.3% to be classified as significant at the 95% confidence level. Serum NfL levels remained stable during the day (p=0.40), whereas a minute variation (6.0-6.6 pg/mL) was observed from day-to-day (p=0.02). Serum NfL is subject to tight homeostatic regulation with none or neglectable semidiurnal and day-to-day variation, but considerable between-subject variation exists. This emphasizes serum NfL as a well-suited biomarker for disease monitoring, but warrants caution when interpreting NfL levels in relation to reference intervals in a diagnosis setting. Furthermore, NfL's tight regulation requires that the analytical variation is kept at a minimum.