Clinical Chemistry and Laboratory Medicine | March 15, 2021

Hviid CVB, Madsen AT and Winther-Larsen A

Clin Chem Lab Med. 2021

DOI: https://doi.org/10.1515/cclm-2020-1276

Abstract

Objectives: The neurofilament light chain (NfL) has emerged as a versatile biomarker for CNS diseases and is approaching clinical use. The observed changes in NfLlevels 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.

Methods: 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 (CVI) and between-subject variation (CVG) were calculated using linear mixed-effects models.

Results: The overall median value of NfL was 6.3 pg/mL(range 2.1–19.1). The CVI was 3.1% and the CVGwas 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).

Conclusions: 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.

This study was performed using the Quanterix HD-1 Analyzer.