Neurofilament light chain - matrix comparison and long-term stability in frozen serum

Neurofilament light chain (NfL) is a sensitive biomarker of neuronal damage and degeneration increasingly used both in research and clinical practice. We aimed to investigate the relationship between NfL concentration in cerebrospinal fluid (CSF), serum, and lithium-heparin plasma samples, and the storage stability of NfL in serum at -20 °C.

Serum and lithium-heparin plasma were compared by adding an extra lithium-heparin tube to routine serum NfL requisitions in our hospital until 50 samples were collected. Serum and CSF NfL were compared by extracting results of 955 paired samples from Danish hospitals taken within four hours of each other and analysed in our hospital laboratory. The stability of serum NfL during storage at -20 °C was assessed in 10 samples from the department of neurology, with repeated measurements performed over 12 months.

Very strong correlations were observed between serum and lithium-heparin plasma (Spearman's rho = 0.98) and between serum and CSF (Spearman's rho = 0.80). A small positive bias of 3.7 % was found for lithium-heparin plasma versus serum, while the median CSF/serum ratio was 54.5 (range: 1.6-385.6). In both comparisons, considerable variability across individual sample pairs was observed, independent of NfL concentration. In the stability study, the mean change from baseline was -7.1 % (95 %CI: -1.7 %; -12.6 %) after 12 months at -20 °C.

NfL concentrations in different matrices were highly correlated, but due to variability across pairs, we recommend using the same matrix to monitor individual patients. Serum NfL concentrations remained stable during 12 months at -20 °C.