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• W3188791636 abstract "α-Synucleinopathies are a group of neurological disorders including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Due to clinical overlaps, accurate discrimination between different types of α-synucleinopathies is challenging. In addition, there is a lack of diagnostic markers in less-invasive body fluids, such as plasma, in this group of diseases. A previous study already analyzed neurofilament light chain (NfL) levels in the cerebrospinal fluid (CSF) of α-synucleinopathies. Holmberg et al1 reported elevated NfL levels in CSF from patients with MSA compared with patients with PD, suggesting NfL as a potential CSF marker for reflecting neuronal/axonal damage in α-synucleinopathies. A meta-analysis of 9 studies about CSF NfL levels in patients with MSA reported an increase of NfL levels in patients with MSA compared with patients with PD, suggesting NfL as a potential marker to distinguish between these 2 diagnoses.2 Our aim in the present study was the analysis of NfL concentrations in plasma of different types of α-synucleinopathies by using an ultrasensitive detection system, single molecule array (SIMOA). We subjected plasma samples from patients with PD, DLB, and MSA (for clinical data, see Table S1) to SIMOA assay analysis (Supplementary Material). Measurement of NfL levels in plasma revealed that patients with DLB and MSA contained a significantly higher amount of NfL compared with patients with PD or the control group (Fig. 1A). To determine the diagnostic accuracy of plasma NfL, we combined the DLB and MSA groups (non-PD synucleinopathies) and conducted receiver operating characteristic (ROC) curve analyses using the Graph Pad Prism 6.0.1 software. We grouped patients with DLB and MSA to obtain statistically more powerful values (Supplementary Material). Interestingly, ROC curve analysis suggested plasma NfL with area under the curve (AUC) values between 0.88 and 0.90 (P < 0.0001) as a promising marker to distinguish between non-PD synucleinopathies and PD as well as between non-PD synucleinopathies and controls (Fig. 1B,C). Splitting of non-PD synucleinopathies into DLB and MSA (lower accuracy because of lower numbers per group) resulted in AUCs of 0.88 to 0.89 for DLB and slightly higher AUCs of 0.91 to 0.92 for MSA (Fig. S1A–D). Until now, there are only few studies that investigated NfL levels in the plasma of α-synucleinopathies by using ultrasensitive detection systems (Table S2). A total of 2 studies observed an increased NfL level in patients with MSA compared with patients with PD and controls by using a SIMOA-based homebrew assay3, 4 but samples from patients with DLB were not included. Depending on the cohort, Hansson et al3 obtained AUC values between AUC 0.8 and 0.9 to distinguish between MSA and PD, which are comparable with our NfL data. Interestingly, we additionally identified elevated plasma NfL levels in patients with DLB that are not distinguishable from patients with MSA. A limitation of this analysis is the relatively small number of available DLB and MSA cases that impeded a proper calculation of diagnostic accuracy. Therefore, a confirmation of our observations in larger cohorts is required. In conclusion, our study suggests plasma NfL as a potential diagnostic marker to discriminate non-PD synucleinopathies from patients with PD and controls, which has prognostic and therapeutic value for these patients. The study has been approved by local ethic committee of the University Medicine Göttingen: No. 19/11/09 “Liquormarker als Prädiktoren für die Entwicklung einer Demenz bei Patienten mit Morbus Parkinson, Demenz mit Lewy-Körperchen und Morbus Alzheimer” and No. 13/11/12 “LIX–Liquormarker zur Frühdiagnose und Krankheitsprogression bei Patienten mit Parkinson-Syndromen und Motorneuronerkrankungen.” All authors have read the manuscript and have indicated consent for publication. This project was supported by the Alzheimer Forschung Initiative Project 20026. Open Access funding enabled and organized by Projekt DEAL. The data that support the findings of this study are available from the corresponding author upon reasonable request. (1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Critically revised the manuscript, C. Review and Critique. M.S.: 1A, 1B, 1C, 2A, 2B, 3A S.Z.: 1C, 2A,,2B, 3A, A.VP.: 1B, 3C K.G.: 3C D.V.: 3C P.L.: 1B 3C F.L.: 2C,3C P.H. 2C, 3C F.M.: 2C,3C I.Z.: 1A, 1B,; 2A, 2C, 3B All authors declare that there are no financial disclosures or any conflicts of interest. Table S1. Supporting Information Table S2. Plasma neurofilament light chain as a biomarker for α synucleinopathies. Figure S1. Receiver operating characteristic (ROC) curve analysis of plasma neurofilament light chain levels in patients. (A–D) ROC analyses were performed with the plasma neurofilament light chain concentrations obtained from patients with dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Diagnostic accuracy was assessed with ROC-derived area under the curve values (with 95% confidence intervals) for the discrimination of (A) DLB from Parkinson's disease (PD), (B) of DLB from controls, (C) of MSA from PD, and (D) MSA from controls. Appendix S1. Supporting Information Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article." @default.
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• W3188791636 title "Validation of <scp>Plasma</scp> Neurofilament Light Chain as a Marker for <scp>α‐Synucleinopathies</scp>" @default.
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