Blood neurofilament light chain in Parkinson disease and atypical parkinsonisms

Abstract

Background: Neurofilament light chain (NfL), an index of neuroaxonal injury, is a promising diagnostic and prognostic fluid biomarker with high translational value in many neurodegenerative disorders. Blood NfL measurement has been an exciting and active field of research in idiopathic Parkinson disease (PD) and atypical parkinsonisms. However, blood NfL levels in these parkinsonisms from existing literature were inconsistent. No comprehensive meta-analysis has ever been conducted. Methods: Three major biomedical electronic databases PubMed, Embase, and Web of Science were comprehensively searched from inception to July 10, 2020. This protocol will be prepared based on the guidelines recommended by the statement of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). Original observational studies that measured blood (serum/plasma) NfL concentrations in patients with parkinsonisms (multiple system atrophy [MSA], progressive supranuclear palsy [PSP], corticobasal syndrome [CBS], and dementia with Lewy bodies [DLB]), and healthy controls (HCs) will be included. Quality assessment of the included studies will be performed using the Newcastle Ottawa Scale (NOS). Meta-analyses will be conducted using the STATA software version 13.0. The standardized mean differences as the measure of effect size and 95% confidence intervals were calculated for each comparison of blood NfL levels. Heterogeneity analysis, sensitivity analysis, publication bias, subgroup analysis, and meta-regression analysis will be carried out to test the robustness of the results. Results: The meta-analysis will obtain the effect sizes of blood NfL levels in the following comparisons: PD versus HC, MSA versus HC, PSP versus HC, CBS versus HC, DLB versus HC, MSA versus PD, PSP versus PD, CBS versus PD, and DLB versus PD. Conclusions: The present meta-analysis will provide the quantitative evidence of NfL levels in idiopathic PD and atypical parkinsonisms, hoping to facilitate differential diagnoses in clinical practice. Registration number: INPLASY202070091.

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“…[7,8] These proteins are synthesized in the body of the neuron and assembled into intermediate filaments in the axon, where they provide stability. [9] Many studies indicate that high levels of pNfL in CSF have been found in different neuroinflammatory and neurodegenerative diseases, such as dementia, [10] Alzheimer's disease (AD), [11] Parkinsonian disorders, [12] and amyotrophic lateral sclerosis. [13] The level of pNfL is higher in AD patients than healthy populations and is also associated with disease progression.…”

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“…One of the most promising biomarkers for assessing the risk of neurological deterioration is initial levels of serum neurofilament light chain (NfL), a member of the family of neurofilament proteins that maintains the structural integrity of neuronal cytoskeleton. NfL is released into cerebrospinal fluid and blood during CNS injury and, as such, is a highly reliable liquid biomarker for neuroaxonal injury and for monitoring the progression of various neurodegenerative conditions (e.g., Parkinson's disease, multisystem atrophy, Alzheimer disease) and neuroinflammatory disorders (e.g., multiple sclerosis) [60][61][62][63][64]. In WD, positive correlations have been observed between sNfL levels and the severity of neurological disease including neurological phenotype (compared to hepatic and asymptomatic) and neurological disease severity scale (UWDRS) [27].…”

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