CSF Biomarkers for Early Diagnosis of Synucleinopathies: Focus on Idiopathic RBD

  • Claudio Liguori
  • Federico Paolini Paoletti
  • Fabio Placidi
  • Roberta Ruffini
  • Giulia Maria Sancesario
  • Paolo Eusebi
  • Nicola Biagio Mercuri
  • Lucilla Parnetti
Sleep (M Thorpy and M Billiard, Section Editors)
Part of the following topical collections:
  1. Topical Collection on Sleep


Purpose of Review

Idiopathic REM sleep behavior disorder (iRBD) is one of the most significant prodromal manifestations of synucleinopathies. Different predictive biomarkers for iRBD conversion have been investigated, but scarce data are present in literature about the predictive role of cerebrospinal fluid (CSF) biomarkers. In this review, we focus on CSF biomarkers in patients with both iRBD and RBD associated with synucleinopathies to explore their potential predictive power.

Recent Findings

Recent studies revealed that CSF α-synuclein levels are higher in Parkinson’s disease (PD) patients with RBD compared to those without RBD, even if α-synuclein does not seem to predict conversion of iRBD into PD. In the Parkinson Progression Marker Initiative (PPMI) cohort, early PD patients with RBD show lower CSF Aβ42 levels, which predict faster cognitive decline. CSF prion protein and inflammatory biomarkers have been also investigated in RBD and synucleinopathies with controversial results.


A variety of CSF biomarkers are promising candidate for predicting iRBD conversion into synucleinopathies. Further studies are needed in iRBD patients followed for several years in order to observe the phenoconversion in synucleinopathies and to elucidate the possible role of CSF biomarkers as predictive biomarkers of conversion.


Idiopathic RBD CSF Biomarkers Synucleinopathy Neurodegeneration 


Compliance with Ethical Standards

Conflict of Interest

Paolo Eusepi, Claudio Liguori, Nicola Biagio Mercuri, Federico Paolini Paoletti, Lucilla Parnetti, Fabio Placidi, Roberta Ruffini and Giulia Maria Sancesario each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Claudio Liguori
    • 1
  • Federico Paolini Paoletti
    • 2
  • Fabio Placidi
    • 1
  • Roberta Ruffini
    • 1
  • Giulia Maria Sancesario
    • 3
  • Paolo Eusebi
    • 2
  • Nicola Biagio Mercuri
    • 3
    • 4
  • Lucilla Parnetti
    • 2
  1. 1.Sleep Medicine Centre, Department of Systems MedicineUniversity of Rome ‘Tor Vergata’RomeItaly
  2. 2.Section of Neurology, Department of MedicineUniversity of PerugiaPerugiaItaly
  3. 3.IRCCS Fondazione Santa LuciaRomeItaly
  4. 4.Neurology Unit, Department of Systems MedicineUniversity of Rome “Tor Vergata”RomeItaly

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