Biomarkers of conversion to α-synucleinopathy in isolated rapid-eye-movement sleep behaviour disorder

Mitchell G. Miglis, Charles H. Adler, Elena Antelmi, Dario Arnaldi, Luca Baldelli, Bradley F. Boeve, Matteo Cesari, Irene Dall'Antonia, Nico J. Diederich, Kathrin Doppler, Petr Dušek, Raffaele Ferri, Jean François Gagnon, Ziv Gan-Or, Wiebke Hermann, Birgit Högl, Michele T. Hu, Alex Iranzo, Annette Janzen, Anastasia KuzkinaJee Young Lee, Klaus L. Leenders, Simon J.G. Lewis, Claudio Liguori, Jun Liu, Christine Lo, Kaylena A. Ehgoetz Martens, Jiri Nepozitek, Giuseppe Plazzi, Federica Provini, Monica Puligheddu, Michal Rolinski, Jan Rusz, Ambra Stefani, Rebekah L.S. Summers, Dallah Yoo, Jennifer Zitser, Wolfgang H. Oertel

Research output: Contribution to journalArticle


Patients with isolated rapid-eye-movement sleep behaviour disorder (RBD) are commonly regarded as being in the early stages of a progressive neurodegenerative disease involving α-synuclein pathology, such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Abnormal α-synuclein deposition occurs early in the neurodegenerative process across the central and peripheral nervous systems and might precede the appearance of motor symptoms and cognitive decline by several decades. These findings provide the rationale to develop reliable biomarkers that can better predict conversion to clinically manifest α-synucleinopathies. In addition, biomarkers of disease progression will be essential to monitor treatment response once disease-modifying therapies become available, and biomarkers of disease subtype will be essential to enable prediction of which subtype of α-synucleinopathy patients with isolated RBD might develop.

Original languageEnglish (US)
Pages (from-to)671-684
Number of pages14
JournalThe Lancet Neurology
Issue number8
StatePublished - Aug 1 2021

Bibliographical note

Funding Information:
CHA reports personal fees from Acadia, Acorda, Amneal, Axovant, Jazz, Lundbeck, Neurocrine, Scion, and Sunovion, outside the submitted work. DA reports consulting fees from Fidia and Bioprojet. BFB reports personal fees from the Scientific Advisory Board-Tau Consortium and grants from Biogen, NIH, the Mangurian Foundation, Alector, the Little Family Foundation, the Turner Family, and EIP Pharma, outside the submitted work. PD reports grants from the Czech Ministry of Health, the Czech Science Foundation, the EU's Horizon 2020 research and innovation programme, and personal fees from BenevolentAI Bio, Retrophin, and Alexion Pharmaceuticals, outside the submitted work. RF reports grants from the Italian Ministry of Health, during the conduct of the study. J-FG reports grants from the Canadian Institutes of Health Research and the Canada Research Chair, during the conduct of the study. ZG-O reports grants from the Michael J Fox Foundation, Parkinson Canada, the Canadian Consortium on Neurodegeneration in Aging, the Canada First Research Excellence Fund, and personal fees from Lysosomal Therapeutics, Idorsia, Prevail Therapeutics, Deerfield, Inception Sciences (Ventus), Denali, Ono Therapeutics, and Neuron23, outside the submitted work. BH reports personal fees from Axovant, Roche, Takeda, Jazz, BenevolentAI Bio, ONO, AOP Orphan, Inspire, and Novartis, and travel support from Habel Medizintechnik Vienna, during the conduct of the study, and has a patent (“Detection of Leg Movements II” Österreichische Patentanmeldung A50649/2019) pending. MTH reports grants from Parkinson's UK, Oxford Biomedical Research Centre, MJFF, H2020 EU, GE Healthcare, and the PSP association, and personal fees from Biogen, Roche, Curasen Pharmaceuticals Consultancy Honoraria, outside the submitted work. AJ reports a grant from ParkinsonFonds Deutschland, outside the submitted work. CL reports grants from the Oxford NIHR Biomedical Research Centre, outside the submitted work. GP reports personal fees from UCB, Bioprojet, Jazz Pharma, and Idorsia, outside the submitted work. FP reports personal fees from Vanda Pharmaceuticals, Sanofi, Zambon, Fidia, Bial, Eisai Japan, and Italfarmaco, outside the submitted work. MR reports grants from NIHR, during the conduct of the study, and grants from Britannia Pharmaceuticals and Eli Lilly, and non-financial support from IXICO, outside the submitted work. WHO reports grants from ParkinsonFonds Deutschland, the Michael J Fox Foundation, and Deutsche Forschungsgemeinschaft (DFG), during the conduct of the study, and personal fees from Adamas, MODAG, Roche, and UCB, outside the submitted work, and is Hertie-Senior-Research Professor supported by the Charitable Hertie-Foundation. All other authors declare no competing interests.

Funding Information:
BFB was supported by grants (R34 AG056639, P30 AG62677, U01 NS100620) from the US NIH. JR (NU20-08-00445) and PD (NU20-08-00445) were supported by grants from the Czech Health Research Council. WHO was supported by ParkinsonFonds Deutschland. No funding source had any role in the writing of the manuscript or the decision to submit for publication. No authors have been paid to write this Review by a pharmaceutical company or other agency.

Publisher Copyright:
© 2021 Elsevier Ltd

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review


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