IRCCS Fondazione Don Carlo Gnocchi ONLUS, 20148 Milan, Italy.
Sleep Disorders Center, Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy.
Int J Mol Sci. 2023 May 16;24(10):8839. 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.
快速眼动睡眠行为障碍（RBD）与突触核蛋白病的关联性强于其他神经退行性疾病。伴 RBD 的帕金森病（PD）患者运动和认知功能损害更严重；目前尚无 RBD 的生物标志物。α-突触核蛋白寡聚体的突触堆积及其与 SNARE 蛋白的相互作用是 PD 中突触功能障碍的原因。我们验证了血清中神经源性细胞外囊泡（NDEVs）中的寡聚α-突触核蛋白和 SNARE 成分是否可以作为 RBD 的生物标志物。纳入 47 例 PD 患者，并编制 RBD 筛查问卷（RBDSQ）。使用 > 6 分的截断值来定义可能的 RBD（p-RBD）和可能的非 RBD（p non-RBD）。通过免疫捕获从血清中分离 NDEVs，并通过 ELISA 测量寡聚α-突触核蛋白和 SNARE 复合物成分 VAMP-2 和 STX-1。与 p non-RBD PD 患者相比，p-RBD 患者血清中的 NDEVs STX-1A 减少。发现 NDEVs 寡聚α-突触核蛋白与 RBDSQ 总分之间存在正相关（ = 0.032）。回归分析证实，NDEVs 寡聚α-突触核蛋白浓度与 RBD 症状之间存在显著关联（ = 0.033），与年龄、疾病持续时间和运动障碍严重程度无关。我们的研究结果表明，PD-RBD 中的突触核蛋白介导的神经退行性变更为弥漫。NDEVs 寡聚α-突触核蛋白和 SNARE 复合物成分的血清浓度可以作为 RBD 特异性 PD 表型的可靠生物标志物。
