Electrochemical Quantitation of the Glycosylation Level of Serum Neurofilament Light Chain for the Diagnosis of Neurodegeneration: An Interface-Solution Dual-Path Amplification Strategy.

Abstract

Serum neurofilament light chain (NFL), a potential general biomarker for neurodegenerative diseases, is not specific enough to differentiate neurodegenerative diseases from other brain diseases such as cerebral thrombosis (CT). According to the importance of glycosylation in neurodegenerative pathogenesis, the NFL glycosylation level (oNFL/tNFL), defined as the ratio of glycosylated NFL (oNFL) to total NFL (tNFL), may be a more effective index. The major challenge in serum oNFL/tNFL detection is the ultra-low abundance of both NFL forms. In this paper, we achieved a convenient one-step electrochemical quantitation of oNFL/tNFL based on an interface-solution dual-path amplification strategy. Two amplified electrochemical signals─the reduction of Cu2+ from adsorbed porous nanoparticles on the sensor interface and the reduction of O2 from horseradish peroxidase-catalyzed H2O2 disproportionation in solution─were adopted to quantify tNFL and oNFL, respectively. The electrochemical sensor displayed good sensitivity, selectivity, and reproducibility. The dynamic range is 1-25 pg mL-1 for tNFL and 0.25-25 pg mL-1 for oNFL, respectively. By analyzing the clinic serum samples, for the first time, our work provided the abundance of oNFL in human serum and revealed that the oNFL/tNFL is effective not only in differentiating three kinds of brain damage patients from healthy people but also in differentiating neurodegeneration from non-neurodegeneration CT patients. As a general biomarker, the oNFL/tNFL is more specific than NFL, which is hoped to be a new and valid indicator for the diagnosis, progression, prediction, and treatment evaluation of neurodegenerative diseases.