Intraindividual Neurofilament Dynamics in Serum Mark the Conversion to Sporadic Parkinson's Disease

Background and Objectives With disease‐modifying treatment strategies on the horizon, stratification of individual patients at the earliest stages of Parkinson's disease (PD) is key—ideally already at clinical disease onset. Blood levels of neurofilament light chain (NfL) provide an easily acce...

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Published inMovement disorders Vol. 35; no. 7; pp. 1233 - 1238
Main Authors Wilke, Carlo, Santos, Marcia Cristina Teixeira, Schulte, Claudia, Deuschle, Christian, Scheller, Dieter, Verbelen, Moira, Brockmann, Kathrin, Thaler, Anna‐Katharina, Sünkel, Ulrike, Roeben, Benjamin, Bujac, Sarah, Metzger, Florian G., Maetzler, Walter, Costa, Andre Nogueira, Synofzik, Matthis, Berg, Daniela
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 01.07.2020
Wiley Subscription Services, Inc
Subjects
biomarker
Biomarkers
Blood levels
Humans
Intermediate Filaments
Longitudinal studies
longitudinal study
Movement disorders
Neurodegenerative diseases
neurofilament light chain (NfL)
Neurofilament Proteins
Parkinson Disease
Parkinson's disease
Parkinson's disease (PD)
Precision medicine
premanifest disease
Prodromal Symptoms
serum
single molecule array (Simoa) technique
single molecule array (Simoa) technique
neurofilament light chain (NfL)
Parkinson's disease (PD)
prodromal symptoms
premanifest disease
longitudinal study
biomarker
serum
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ISSN0885-3185
1531-8257
1531-8257
DOI10.1002/mds.28026

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Summary:Background and Objectives With disease‐modifying treatment strategies on the horizon, stratification of individual patients at the earliest stages of Parkinson's disease (PD) is key—ideally already at clinical disease onset. Blood levels of neurofilament light chain (NfL) provide an easily accessible fluid biomarker that might allow capturing the conversion from prodromal to manifest PD. Methods We assessed longitudinal serum NfL levels in subjects converting from prodromal to manifest sporadic PD (converters), at‐risk subjects, and matched controls (72 participants with ≈4 visits), using single‐molecule array (Simoa) technique. Results While NfL levels were not increased at the prodromal stage, subjects converting to the manifest motor stage showed a significant intraindividual acceleration of the age‐dependent increase of NfL levels. Conclusions The temporal dynamics of intraindividual NfL blood levels might mark the conversion to clinically manifest PD, providing a potential stratification biomarker for individual disease onset in the advent of precision medicine for PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Bibliography:This work was supported by the BioPharma initiative Neuroallianz (project D13 B) of the German Federal Ministry for Education and Research (Grants 16GW0066K and 16GW0067 to W.M.), the Horizon 2020 research and innovation program (Grant 779257 Solve‐RD to M.S.), the National Ataxia Foundation (grant to C.W. and M.S.), the Wilhelm Vaillant Stiftung (grant to C.W.), and UCB Pharma GmbH (Monheim am Rhein, Germany).
Relevant conflicts of interests/financial disclosures
UCB Biopharma SPRL and UCB Pharma SA provided support in the form of salaries for authors MCTdS, DS, MV, SB and ANdC, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. MS received speaker's honoraria and research support from Actelion Pharmaceuticals, unrelated to the current project and manuscript. BR received travel expenses and speaker honoraria from BIAL Germany. FM received research support from Storz medical AG, Ministry of social affairs Baden‐Württemberg and the Center of Psychiatry Südwürttemberg. WM receives or received funding from the European Union, the German Federal Ministry of Education of Research, Michael J. Fox Foundation, Robert Bosch Foundation, Neuroalliance, Lundbeck and Janssen. He received speaker honoraria from Abbvie, Bayer, GlaxoSmithKline, Licher MT, Rölke Pharma and UCB, was invited to Advisory Boards of Abbvie, Biogen, Lundbeck and Market Access & Pricing Strategy GmbH, and is an advisory board member of the Critical Path for Parkinson's Consortium. He serves as the co‐chair of the MDS Technology Task Force. DB served on the advisory boards of Biogen, BIAL, Lundbeck, UCB Pharma, received honoraria from AbbVie, Biogen, BIAL, Lundbeck, UCB Pharma, Zambon, Desitin, GE, and received grants from Janssen Pharmaceutica, German Parkinson's Disease Association (dPV), Federal Ministry for Economic Affairs and Energy (BMWi), Federal Ministry of Education and Research (BMBF), EU, Parkinson Fonds Deutschland, UCB Pharma, Novartis Pharma, Lundbeck, and Damp foundation, all unrelated to the manuscript. The other authors declare no competing financial interests.
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ISSN:0885-3185
1531-8257
1531-8257
DOI:10.1002/mds.28026