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Serum neurofilament light is increased in multiple system atrophy of cerebellar type and in repeat-expansion spinocerebellar ataxias: a pilot study

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Abstract

Blood biomarkers in degenerative ataxias are still largely missing. Here, we aimed to provide piloting proof-of-concept that serum Neurofilament light (NfL) could offer a promising peripheral blood biomarker in degenerative ataxias. Specifically, as a marker of neuronal damage, NfL might (1) help to differentiate multiple system atrophy of cerebellar type (MSA-C) from sporadic adult-onset ataxia (SAOA), and (2) show increases in repeat-expansion spinocerebellar ataxias (SCAs) which might be amenable to treatment in the future. To explore these two hypotheses, we measured serum NfL levels by single-molecule array (Simoa) technique in 115 subjects, comprising patients with MSA-C (n = 25), SAOA (n = 25), the most frequent repeat-expansion SCAs (SCA 1, 2, 3 and 6) (n = 20), and age-matched controls (n = 45). Compared to controls, NfL was significantly increased in MSA-C, with levels significantly higher than in SAOA (AUC = 0.74 (0.59–0.89), mean and 95% confidence interval, p = .004). NfL was also significantly increased in SCA patients as compared to controls (AUC = 0.91 (0.81–1.00), p < .001), including NfL increases in SCA1 and SCA3. These findings provide first proof-of-concept that NfL might provide a promising peripheral biomarker in degenerative ataxias, e.g. supporting the differentiation of MSA-C from SAOA, and indicating neuronal damage in repeat-expansion SCAs.

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Acknowledgements

Biosamples were obtained from the Neuro-Biobank of the University of Tübingen, Germany, which is supported by the University of Tübingen, the Hertie Institute for Clinical Brain Research (HIH) and the German Center for Neurodegenerative Diseases (DZNE). MS was supported by the Else Kröner-Fresenius-Stiftung.

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Author notes

  1. Jens Kuhle and Matthis Synofzik share last authorship.

Authors and Affiliations

  1. Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research and Center of Neurology, University of Tübingen, Hoppe-Seyler-Str. 3, 72076, Tübingen, Germany

    Carlo Wilke, Friedemann Bender, Stefanie N. Hayer, Kathrin Brockmann, Ludger Schöls & Matthis Synofzik

  2. German Center for Neurodegenerative Diseases (DZNE), University of Tübingen, Tübingen, Germany

    Carlo Wilke, Friedemann Bender, Stefanie N. Hayer, Kathrin Brockmann, Ludger Schöls & Matthis Synofzik

  3. Neurologic Clinic and Policlinic, Departments of Medicine, Biomedicine and Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland

    Jens Kuhle

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  1. Carlo Wilke
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Contributions

CW: design and conceptualisation of the study, acquisition of data, analysis of the data, drafting and revision of the manuscript. FB: acquisition of data, revision of the manuscript. SH: acquisition of data, revision of the manuscript. KB: acquisition of data, revision of the manuscript. LS: acquisition of data, revision of the manuscript. JK: acquisition and analysis of data, design and conceptualisation of measurements, revision of the manuscript. MS: design and conceptualisation of the study, acquisition of data, drafting and revision of the manuscript.

Corresponding author

Correspondence to Matthis Synofzik.

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Conflicts of interest

JK’s institution (University Hospital Basel) received in the last 3 years and used exclusively for research support: consulting fees from Novartis, Protagen AG; speaker fees from the Swiss MS Society, Biogen, Novartis, Roche, Genzyme; travel expenses from Merck Serono, Novartis; grants from ECTRIMS Research Fellowship Programme, University of Basel, Swiss MS Society, Swiss National Research Foundation, Bayer (Switzerland) AG, Genzyme, Novartis. MS received speaker’s honoraria and research support from Actelion Pharmaceuticals, unrelated to the current project and manuscript. The other authors declare no competing financial interests.

Ethical statements

The university’s ethics committee approved the study; the methods were carried out in accordance with the relevant guidelines and regulations.

Informed consent

All the subjects gave a written informed consent prior to participation.

Data availability

The datasets analysed in the current study are available from the corresponding author on reasonable request.

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Wilke, C., Bender, F., Hayer, S.N. et al. Serum neurofilament light is increased in multiple system atrophy of cerebellar type and in repeat-expansion spinocerebellar ataxias: a pilot study. J Neurol 265, 1618–1624 (2018). https://doi.org/10.1007/s00415-018-8893-9

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  • DOI: https://doi.org/10.1007/s00415-018-8893-9

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