Novel biomarker signatures for idiopathic REM sleep behavior disorder: A proteomic and system biology approach

Stefania Mondello, Firas Kobeissy, Yehia Mechref, Jingfu Zhao, Farid R Talih, Filomena Cosentino, Elena Antelmi, Monica Moresco, Giuseppe Plazzi, Raffaele Ferri

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes.

METHODS: Serum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography-mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD.

RESULTS: We identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology.

CONCLUSIONS: Our results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.

Original languageEnglish
JournalNeurology
DOIs
Publication statusE-pub ahead of print - Sep 26 2018

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