Stefania Mondello1, Firas Kobeissy2, Yehia Mechref2, Jingfu Zhao2, Farid R Talih2, Filomena Cosentino2, Elena Antelmi2, Monica Moresco2, Giuseppe Plazzi2, Raffaele Ferri2. 1. From Oasi Research Institute (IRCCS) (S.M., F.C., R.F.), Troina; University of Messina (S.M.), Italy; McKnight Brain Institute (F.K.), University of Florida, Gainesville; American University of Beirut (F.K., F.R.T.), Lebanon; Texas Tech University (Y.M., J.Z.), Lubbock; and University of Bologna (E.A., M.M., G.P.), Italy. stm_mondello@hotmail.com. 2. From Oasi Research Institute (IRCCS) (S.M., F.C., R.F.), Troina; University of Messina (S.M.), Italy; McKnight Brain Institute (F.K.), University of Florida, Gainesville; American University of Beirut (F.K., F.R.T.), Lebanon; Texas Tech University (Y.M., J.Z.), Lubbock; and University of Bologna (E.A., M.M., G.P.), Italy.
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.
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.
Authors: 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 Kuzkina; Jee-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 Journal: Lancet Neurol Date: 2021-08 Impact factor: 44.182