Yan X M, Li P J, Li W, Wang X M, Yu S
Department of Functional Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053,China.
Department of Neurobiology, Xuanwu Hospital, Capital Medical University, Beijing 100053,China.
Zhonghua Yi Xue Za Zhi. 2023 Oct 10;103(37):2933-2939. doi: 10.3760/cma.j.cn112137-20230607-00957.
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. 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. 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 (<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] (<0.001). The sensitivity and specificity of RBC-O-α-Syn in distinguishing PD patients and HC subjects were 87.16% (95%: 82.87%-90.50%) and 86.10% (95%: 82.38%-89.14%), with an AUC of 0.933 (95%: 0.914-0.951), and the sensitivity and specificity in distinguishing MSA patients and HC subjects were 85.88% (95%: 76.93%-91.74%) and 81.39% (95%: 77.30%-84.89%), with an AUC of 0.921 (95%: 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, =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 (>0.05). In addition, RBC-O-α-Syn content was positively correlated with UPDRS Ⅲ (=0.18, =0.002) and the score of rapid eye movement sleep behavior disorder questionnaire(Hong Kong) (RBDQ-HK)(=0.19, <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 >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 >0.05). 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.
分析帕金森病(PD)和多系统萎缩(MSA)患者红细胞中α-突触核蛋白寡聚体(O-α-Syn)的含量及其与临床症状的相关性。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和神经内科招募了296例PD患者和85例MSA患者。同期从北京老龄化纵向研究社区队列中招募了403名健康对照(HC)。采用酶联免疫吸附测定(ELISA)法检测红细胞O-α-Syn水平。采用单变量线性回归模型分析RBD-O-α-Syn含量与各种运动和非运动功能评分之间的相关性,如统一帕金森病评定量表(UPDRS)Ⅲ、统一多系统萎缩评定量表(UMSARS)Ⅲ、简易精神状态检查表(MMSE)、快速眼动睡眠障碍问卷-香港版(RBDQ-HK)和蒙特利尔认知评估量表(MoCA)。采用受试者操作特征(ROC)曲线评估红细胞O-α-Syn在区分PD和MSA患者与HC受试者时的特异性、敏感性和曲线下面积(AUC)。HC受试者的平均年龄为(70±8)岁,PD患者的平均年龄为(64±9)岁,其中震颤为主型PD(TD-PD)115例(38.9%),姿势不稳为主型PD(PIGD-PD)132例(44.6%),H-Y分期2期患者142例(48.0%)。UPDRSⅢ评分为31.2±17.8。MSA患者的平均年龄为(64±9)岁,UMSARSⅡ平均评分为18.9±10.3。PD和MSA患者的非运动症状与HC受试者有显著差异(<0.001)。PD组[(50±17)ng/mg]和MSA组[(52±19)ng/mg]红细胞O-α-Syn水平显著高于HC组[(21±10)ng/mg](<0.001)。红细胞O-α-Syn区分PD患者和HC受试者的敏感性和特异性分别为87.16%(95%:82.87%-90.50%)和86.10%(95%:82.38%-89.14%),AUC为0.933(95%:0.914-0.951),区分MSA患者和HC受试者的敏感性和特异性分别为85.88%(95%:76.93%-91.74%)和81.39%(95%:77.30%-84.89%),AUC为0.921(95%:0.884-0.957)。快速眼动睡眠行为障碍(RBD)的PD患者红细胞O-α-Syn水平高于无RBD的PD患者[(53±16)ng/mg对(48±17)ng/mg,=0.029]。女性PD患者和HC受试者红细胞O-α-Syn含量高于男性,但不同年龄和病程受试者之间无显著差异(>0.05)。此外,红细胞O-α-Syn含量与UPDRSⅢ(=0.18,=0.002)和快速眼动睡眠行为障碍问卷(香港版)(RBDQ-HK)评分(=0.19,<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)评分均无相关性(均>0.05)。MSA患者红细胞O-α-Syn含量与UMSARSⅡ、NMSS、MMSE、MoCA、HAMD、HAMA均无相关性(均>0.05)。PD和MSA患者红细胞O-α-Syn水平显著升高。红细胞O-α-Syn水平与UPDRSⅢ和RBDQ-HK评分呈正相关。