Oligomeric Alpha-Synuclein and STX-1A from Neural-Derived Extracellular Vesicles (NDEVs) as Possible Biomarkers of REM Sleep Behavior Disorder in Parkinson's Disease: A Preliminary Cohort Study

• Published in: International journal of molecular sciences 2023-05, Vol.24 (10), p.8839
• Main Authors: Meloni, Mario, Agliardi, Cristina, Guerini, Franca Rosa, Saibene, Francesca Lea, Milner, Anna Vera, Zanzottera, Milena, Bolognesi, Elisabetta, Puligheddu, Monica, Figorilli, Michela, Navarro, Jorge, Clerici, Mario
• Format: Article
• Language: English
• Subjects: Age; alpha-Synuclein - metabolism; Analysis; Behavior disorders; Biological markers; Biomarkers; Cohort analysis; Cohort Studies; Communication; Enzyme-linked immunosorbent assay; exosomes; Extracellular vesicles; Humans; Impairment; Medical research; Medicine, Experimental; Mental illness; Movement disorders; Neurodegeneration; oligomeric alpha-synuclein; Oligomers; Parkinson Disease - metabolism; Parkinson's disease; Parkinson’s disease (PD); Patients; Proteins; REM sleep; REM sleep behavior disorder (RBD); REM Sleep Behavior Disorder - diagnosis; REM Sleep Behavior Disorder - etiology; REM Sleep Behavior Disorder - metabolism; Signs and symptoms; Sleep; Sleep disorders; SNAP receptors; Surveys and Questionnaires; Synuclein; Vesicles
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24108839

REM sleep behavior disorder (RBD) has a tighter link with synucleinopathies than other neurodegenerative disorders. Parkinson's Disease (PD) patients with RBD have a more severe motor and cognitive impairment; biomarkers for RBD are currently unavailable. Synaptic accumulation of α-Syn oligomers and their interaction with SNARE proteins is responsible for synaptic dysfunction in PD. We verified whether oligomeric α-Syn and SNARE components in neural-derived extracellular vesicles (NDEVs) in serum could be biomarkers for RBD. Forty-seven PD patients were enrolled, and the RBD Screening Questionnaire (RBDSQ) was compiled. A cut-off score > 6 to define probable RBD (p-RBD) and probable non-RBD (p non-RBD) was used. NDEVs were isolated from serum by immunocapture, and oligomeric α-Syn and SNARE complex components VAMP-2 and STX-1 were measured by ELISA. NDEVs' STX-1A resulted in being decreased in p-RBD compared to p non-RBD PD patients. A positive correlation between NDEVs' oligomeric α-Syn and RBDSQ total score was found ( = 0.032). Regression analysis confirmed a significant association between NDEVs' oligomeric α-Syn concentration and RBD symptoms ( = 0.033) independent from age, disease duration, and motor impairment severity. Our findings suggest that synuclein-mediated neurodegeneration in PD-RBD is more diffuse. NDEVs' oligomeric α-Syn and SNARE complex components' serum concentrations could be regarded as reliable biomarkers for the RBD-specific PD endophenotype.