Cerebrospinal fluid and blood levels of neurofilament light chain in Parkinson disease

Abstract

Background: Parkinson disease (PD) is a common neurodegenerative disorder. Elevations of neurofilament light chain (NfL) concentrations in the cerebrospinal fluid (CSF) and blood are a marker of neuronal/axonal injury and degeneration. However, CSF and blood NfL alterations in patients with PD from existing studies remain inconclusive. To better understand these conflicting data, we will conduct a meta-analysis. Methods: We will comprehensively search PubMed, Embase, and Web of Science databases from each database's inception to 7th June, 2020. This protocol will conform to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols. We will only include original studies published in English that evaluated differences of NfL concentrations in the CSF or blood between idiopathic PD patients and healthy controls. The Newcastle-Ottawa Scale will be used to evaluate the quality of the included studies. Meta-analyses will be carried out using the STATA software version 13.0. Between-group difference of NfL concentrations in the CSF and blood will be expressed as the weighted standardized mean difference. A random-effects model will be used. Supplementary analyses, such as heterogeneity analysis, sensitivity analysis, publication bias, subgroup analysis, and meta-regression analysis will be performed. Results: The meta-analysis will provide the differences of NfL concentrations in the CSF and blood between patients with PD and healthy controls and will show the magnitudes of their effect sizes. Conclusions: This meta-analysis will provide the evidence of NfL concentrations in the CSF and blood in PD and we hope that our study has an important impact on clinical practice. Registration number: INPLASY202060025

The Role of Serum Levels of Neurofilament Light (NfL) Chain as a Biomarker in Friedreich Ataxia

“… Temporal course of changes in FRDA. Diagram illustrating the contrasting temporal course of clinical changes in FRDA along with serum NfL levels over time (amalgamated from Bridel et al, 2019 ; Del Prete et al, 2020 ; Wang et al, 2020 ). Clinical changes are presented based on the clinical course of an early onset individual (onset between ages 5−10).…”

“…Interestingly, cardiac troponin levels are elevated in FRDA serum during the period of hypertrophic disease, long before cardiomyocytes die and cardiac fibrosis develops (Friedman et al, 2013;Plehn et al, 2018;Legrand et al, 2020). Such elevated levels Bridel et al, 2019;Del Prete et al, 2020;Wang et al, 2020). Clinical changes are presented based on the clinical course of an early onset individual (onset between ages 5−10).…”

“…Such markers can capture subclinical changes in a rapid manner and show evidence of target engagement in clinical trials in slowly progressive neurological disorders. In other neurological disorders, including Multiple Sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD), neurofilament light chain levels (NfL) in body fluids such as serum, plasma or CSF may provide a biomarker for tracking disease activity including progression (Bridel et al, 2019 ; Forgrave et al, 2019 ; Aktas et al, 2020 ; Del Prete et al, 2020 ; Milo et al, 2020 ; Thebault et al, 2020 ; Wang et al, 2020 ). Neurofilaments are cytoskeletal proteins located in both the peripheral and central nervous system, particularly in larger myelinated axons.…”

Biomarkers and the Role of α-Synuclein in Parkinson’s Disease

“…They found decreased CSF levels of glutamate and taurine and increased CSF levels of tyrosine; decreased serum/plasma levels of aspartate, serine, tryptophan, and lysine, and increased serum/plasma proline and homocysteine levels (Jiménez-Jiménez et al, 2020 ). Taken together, these markers, and many other proteins such as circulating microRNAs and neurofilament light (He et al, 2018 ; Khalil et al, 2018 ; van den Berg et al, 2020 ; Wang H. et al, 2020 ), have all been reported to be associated with PD. However, Dos Santos et al ( 2018 ) has also proposed that the potential biomarkers lacked robustness and reproducibility in supporting diagnosis in the early clinical stages of PD; therefore, we still need further validation to confirm these findings.…”