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
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...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8839 |
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| author | Mario Meloni Cristina Agliardi Franca Rosa Guerini Francesca Lea Saibene Anna Vera Milner Milena Zanzottera Elisabetta Bolognesi Monica Puligheddu Michela Figorilli Jorge Navarro Mario Clerici |
| author_facet | Mario Meloni Cristina Agliardi Franca Rosa Guerini Francesca Lea Saibene Anna Vera Milner Milena Zanzottera Elisabetta Bolognesi Monica Puligheddu Michela Figorilli Jorge Navarro Mario Clerici |
| author_sort | Mario Meloni |
| collection | DOAJ |
| description | 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 (<i>p</i> = 0.032). Regression analysis confirmed a significant association between NDEVs’ oligomeric α-Syn concentration and RBD symptoms (<i>p</i> = 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. |
| first_indexed | 2024-03-11T03:39:19Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:39:19Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-278783815f7e4f3ca60c8d89b373ceed2023-11-18T01:42:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410883910.3390/ijms24108839Oligomeric 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 StudyMario Meloni0Cristina Agliardi1Franca Rosa Guerini2Francesca Lea Saibene3Anna Vera Milner4Milena Zanzottera5Elisabetta Bolognesi6Monica Puligheddu7Michela Figorilli8Jorge Navarro9Mario Clerici10IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalySleep Disorders Center, Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, ItalySleep Disorders Center, Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, ItalyIRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalyIRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, ItalyREM 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 (<i>p</i> = 0.032). Regression analysis confirmed a significant association between NDEVs’ oligomeric α-Syn concentration and RBD symptoms (<i>p</i> = 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.https://www.mdpi.com/1422-0067/24/10/8839oligomeric alpha-synucleinextracellular vesiclesexosomesREM sleep behavior disorder (RBD)Parkinson’s disease (PD) |
| spellingShingle | Mario Meloni Cristina Agliardi Franca Rosa Guerini Francesca Lea Saibene Anna Vera Milner Milena Zanzottera Elisabetta Bolognesi Monica Puligheddu Michela Figorilli Jorge Navarro Mario Clerici 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 International Journal of Molecular Sciences oligomeric alpha-synuclein extracellular vesicles exosomes REM sleep behavior disorder (RBD) Parkinson’s disease (PD) |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | oligomeric alpha-synuclein extracellular vesicles exosomes REM sleep behavior disorder (RBD) Parkinson’s disease (PD) |
| url | https://www.mdpi.com/1422-0067/24/10/8839 |
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