Increased CSF NFL in Non-demented Parkinson's Disease Subjects Reflects Early White Matter Damage.

Konrad Rejdak,Ewa Papuć

doi:10.3389/fnagi.2020.00128

Abstract

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with various underlying pathological processes. Until now, no fluid biomarkers have been established for PD. Given recent biochemical and neuroimaging evidence for the presence of white matter damage in PD, which may even precede neuronal loss, we investigated whether neurofilament light (NFL) was increased in the cerebrospinal fluid (CSF) of PD patients in comparison to controls. NFL is located mainly in large myelinated axons, and increased CSF levels of this protein reflect axonal injury. CSF levels of NFL in 58 early PD patients and 28 controls were quantified by ELISA (Uman Diagnostics). Measures of PD severity included disease duration, UPDRS-III, and Hoehn-Yahr stage. Statistically significant differences in CSF NFL levels were found between PD patients and controls [median with interquartile range 524.82 (393.28–678.34) vs. 271.84 (198.09–335.24) ng/l; p < 0.05)]. In PD patients, there were no correlations between CSF NFL level and the measures of disease severity. The CSF NFL turned out to have a high discriminatory value (AUC 0.850) for differentiating between PD subjects and healthy controls, with 84% sensitivity and 85.2% specificity. The study indirectly demonstrates that axonal damage is present in early PD in addition to neuronal loss. Interestingly, white matter damage was observed in non-demented PD patients. In the light of the results of recent MRI studies which confirm early white matter damage in PD, our data may turn out to be potentially useful in the diagnosis of early, or even preclinical, stages of the disease.

Highlights

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with various underlying pathologies
Given recent biochemical and neuroimaging evidence for the presence of white matter damage in PD, which may even precede neuronal loss, we investigated whether neurofilament light (NFL) was increased in the cerebrospinal fluid (CSF) of PD patients in comparison to controls
Significant differences in CSF NFL levels were observed between PD patients and healthy controls; CSF NFL data are presented as median values with interquartile range [524.82 (393.28–678.34) vs. 271.84 (198.09–335.24) ng/l; p < 0.05; Figure 1]

Summary

INTRODUCTION

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with various underlying pathologies. NFL has been considered as a marker of axonal damage in different neurological disorders (Herbert et al, 2015) and, in the light of some recent data (Backstrom et al, 2015), has become of potential interest as a CSF biomarker in PD. While some authors have found increased levels of this biomarker in the CSF of PD patients compared to healthy controls (Backstrom et al, 2015; Oosterveld et al, 2020), many others have observed no differences between these two groups of subjects (Constantinescu et al, 2010; Herbert et al, 2015; Hansson et al, 2017). In the light of recent neuroimaging data (Rektor et al, 2018), CSF NFL could be potentially of interest in the diagnosis of the preclinical stage of PD, if axonal damage does precede gray matter deterioration

MATERIALS AND METHODS

RESULTS

Limitations of the Study

CONCLUSION

ETHICS STATEMENT