Objective: To analyze the content of α-synuclein oligomer(O-α-Syn) in erythrocytes in patients with Parkinson's disease (PD) and multiple system atrophy (MSA) and the correlation with clinical symptoms. Methods: Two hundred and ninety-six PD patients and 85 MSA patients were recruited from the Department of Functional Neurosurgery and Neurology of Xuanwu Hospital, Capital Medical University from July 2020 to October 2021. Four hundred and three healthy controls (HC) were recruited from the Beijing Longitudinal Study of Aging community cohort during the same period. The levels of RBC-O-α-Syn were measured by enzyme-linked immunosorbent assay (ELISA). Univariate linear regression model was used to analyze the correlation between the content of RBD-O-α-Syn and various motor and non-motor functional scores, such as Unified Parkinson Disease Rating Scale (UPDRS) Ⅲ, Unified Multiple System Atrophy Rating Scale (UMSARS) Ⅲ, Mini-Mental State Examination (MMSE), rapid eye movement sleep disorder questionnaire-HongKong(RBDQ-HK) and Montreal Cognitive Assessment (MoCA). Receiver operating characteristic (ROC) curves was used to evaluate the specificity, sensitivity, and the area under the curve (AUC) of RBC-O-α-Syn in distinguishing PD and MSA patients from HC subjects. Results: The average age of HC subjects was (70±8) years old, the average age of PD patients was (64±9) years old, including 115 (38.9%) cases with tremor dominant PD (TD-PD), 132 cases (44.6%) of postural instability disorder predominant PD (PIGD-PD), and 142 cases (48.0%) of patients with H-Y stage 2. UPDRS Ⅲ score was 31.2±17.8. The mean age of MSA patients was (64±9) years, with the mean UMSARS Ⅱ score of 18.9±10.3. The non-motor symptoms of PD and MSA patients were significantly different from those of HC subjects (P<0.001). The levels of RBC-O-α-Syn in PD [(50±17) ng/mg] and MSA [(52±19) ng/mg] were significantly higher than those in HC subjects [(21±10) ng/mg] (P<0.001). The sensitivity and specificity of RBC-O-α-Syn in distinguishing PD patients and HC subjects were 87.16% (95%CI: 82.87%-90.50%) and 86.10% (95%CI: 82.38%-89.14%), with an AUC of 0.933 (95%CI: 0.914-0.951), and the sensitivity and specificity in distinguishing MSA patients and HC subjects were 85.88% (95%CI: 76.93%-91.74%) and 81.39% (95%CI: 77.30%-84.89%), with an AUC of 0.921 (95%CI: 0.884-0.957). The levels of RBC-O-α-Syn in PD patients with rapid eye movement sleep behavior disorder (RBD) were higher than that in PD patients without RBD [(53±16) ng/mg vs (48±17) ng/mg, P=0.029].The content of RBC-O-α-Syn in female PD patients and HC subjects was higher than that in male, but there was no significant difference between subjects of different ages and disease duration (P>0.05). In addition, RBC-O-α-Syn content was positively correlated with UPDRS Ⅲ (r=0.18, P=0.002) and the score of rapid eye movement sleep behavior disorder questionnaire(Hong Kong) (RBDQ-HK)(r=0.19, P<0.001). But there was no correlation with H-Y stage, non-motor symptoms scale (NMSS), MMSE, Moca, Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA) scores (all P>0.05). There was no correlation between RBC-O-α-Syn content and UMSARS Ⅱ, NMSS, MMSE, MoCA, HAMD, HAMA in patients with MSA (all P>0.05). Conclusions: Levels of RBC-O-α-Syn are significantly increased in PD and MSA patients. There are positive correlations between levels of RBC-O-α-Syn and scores of UPDRS Ⅲ and RBDQ-HK.
目的： 分析帕金森病（PD）和多系统萎缩（MSA）患者红细胞中的α-突触核蛋白寡聚体（RBC-O-α-Syn）含量及其与临床症状的相关性。 方法： 收集2020年7月至2021年10月从首都医科大学宣武医院功能神经外科、神经内科招募的PD患者296例，MSA患者85例，同期从北京老年纵向研究社区队列招募健康对照（HC）受试者403名。ELISA测试RBC-O-α-Syn含量。单变量线性回归模型分析各种运动和非运动评分，如帕金森病统一评定量表（UPDRS）Ⅲ、多系统萎缩统一评定量表（UMSARS）Ⅲ、简易智力状态检查量表（MMSE）、快速眼动睡眠行为障碍-香港（RBDQ-HK）及蒙特利尔认知评估量表（MoCA）评分与RBC-O-α-Syn含量的相关性。受试者工作特征（ROC）曲线评估RBC-O-α-Syn区分PD、MSA患者和HC受试者的特异度、灵敏度和曲线下面积（AUC）。 结果： HC组受试者年龄（70±8）岁；PD患者年龄（64±9）岁，其中，震颤为主型PD（TD-PD）115例（38.9%），姿势不稳步态障碍为主型PD（PIGD-PD）132例（44.6%），H-Y分期为2期的患者142例（48.0%）。UPDRS Ⅲ评分为（31.2±17.8）分；MSA患者年龄（64±9）岁，UMSARS Ⅱ评分（18.9±10.3）分。PD和MSA患者的各种非运动症状与HC受试者的差异均有统计学意义（均P<0.001）。PD组患者和MSA组患者RBC-O-α-Syn含量［（50±17）、（52±19）ng/mg］明显高于HC组受试者［（21±10）ng/mg］（均P<0.001）。RBC-O-α-Syn区分PD患者和HC受试者的灵敏度和特异度分别为87.16%（95%CI：82.87%~90.50%）和86.10%（95%CI：82.38%~89.14%），AUC为0.933（95%CI：0.914~0.951），区分MSA患者和HC受试者的灵敏度和特异度分别为85.88%（95%CI：76.93%~91.74%）和81.39%（95%CI：77.30%~84.89%），AUC为0.921（95%CI：0.884~0.957）。PD患者伴随快速眼动睡眠行为障碍（RBD）者的RBC-O-α-Syn含量高于不伴RBD者［（53±16）比（48±17）ng/mg，P=0.029］。MSA患者伴随RBD者的RBC-O-α-Syn含量与不伴随RBD者的差异无统计学意义［（56±17）ng/mg 比（48±20）ng/mg，P=0.070］。RBC-O-α-Syn含量在女性PD患者和HC受试者中高于男性，但在不同年龄和病程的受试者之间差异无统计学意义（P>0.05）。此外，RBC-O-α-Syn含量与UPDRS Ⅲ（r=0.18，P=0.002）、快速眼动睡眠行为障碍问卷-香港（RBDQ-HK）分数（r=0.19，P<0.001）呈正相关，但与H-Y分期、非运动症状量表（NMSS）、MMSE、MoCA、汉密尔顿抑郁量表（HAMD）、汉密尔顿焦虑量表（HAMA）分数无相关性（均P>0.05）。MSA患者的RBC-O-α-Syn含量与UMSARS Ⅱ以及NMSS、MMSE、MoCA、HAMD、HAMA均无相关性（均P>0.05）。 结论： PD和MSA患者RBC-O-α-Syn含量显著增高，PD患者RBC-O-α-Syn含量与UPDRS Ⅲ和RBDQ-HK分数呈正相关。.