Cerebrospinal fluid neurofilament light protein as a diagnostic and prognostic biomarker in mitochondrial diseases with CNS involvement

Abstract

Background: Mitochondrial disorders are a group of clinically and genetically heterogeneous disorders caused by impaired oxidative phosphorylation. At present there are no reliable cerebrospinal fluid (CSF) biomarkers of diagnostic value or prognostic utility with regard to long-term survival. The aim of this study was to assess CSF biomarkers of axonal, astroglial and amyloid metabolism in relation to the genotype, phenotype and disease-related outcomes in pediatric patients with genetically verified mitochondrial disorders. Objective: To assess CSF biomarkers of axonal, astroglial and amyloid metabolism in relation to the genotype, phenotype and disease-related outcomes in pediatric patients with genetically verified mitochondrial disorders. Methods: Our patient-pool was pediatric patients who were referred to the Queen Silvia Children’s Hospital, Sweden during 1984–2014 for suspected mitochondrial disease and underwent clinical, laboratory, neuroimaging, genetic and muscle investigations. We included 52 patients with genetically verified mitochondrial disease and 16 age-matched patients without neurometabolic disease as controls. The biomarkers analyzed in CSF were total-tau, neurofilament light protein (NF-L), glial fibrillary acidic protein, amyloid-β 42 and phosphorylated-tau. Results: The levels of NF-L were significantly increased in patients with mitochondrial diseases compared to age-matched controls (p<0.001). Patients with predominant cortical involvement on brain MRI had significantly higher levels of NF-L compared to those without cortical lesions (p<0.001). The levels of NF-L were significantly correlated to poor survival outcomes (p<0.001). Conclusion: We found that CSF NF-L has both diagnostic and prognostic utility. These preliminary results suggest that NF-L may be used in both clinical and research settings to monitor the progression of patients with mitochondrial disease and help evaluate the effect of novel therapies.