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血浆神经丝蛋白轻链与帕金森病亚型的相关性

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目的 探讨帕金森病(Parkinson disease,PD)患者血浆总α-突触核蛋白(α-synuclein,α-syn)、磷酸化-α-突触核蛋白(phosphorylated α-synuclein,p-α-syn)、神经丝蛋白轻链(neurofilament light chain,NfL)与不同亚型的关系.方法 连续收集2021年9月至2023年1月在南京医科大学附属淮安第一医院神经内科就诊的62例PD患者(PD组),进行H-Y分期(Hoehn-Yahr,H-Y)、统一帕金森病评定量表Ⅲ(unified Parkinson's disease rating scale Ⅲ,UPDRS-Ⅲ)、左旋多巴每日等效剂量(levodopa equivalent daily dosage,LEDD)、简易精神状态量表(mini-mental state examination,MMSE)、帕金森病生活质量问卷 39 项(Parkinson disease quality of life questionnaire 39,PDQ-39)、日常生活活动能力(activities of daily living,ADL)等评分.同期选择年龄、性别匹配的健康志愿者25例作为对照组(HC组).收集临床资料,采集血样标本,利用ELISA技术检测PD组和HC组血浆α-syn、p-α-syn、NfL水平.根据UPDRS-Ⅲ评分将PD患者分为震颤型(tremor dominant,TD;n=27)和少动-强直型(akinetic rigid dominant,AR;n=35).使用 SPSS 25.0 软件进行统计分析,应用 Logistic 回归分析 PD亚型的影响因素,绘制受试者工作特征曲线(receiver operating characteristic,ROC)判断血浆NfL在临床上区分PD的TD与AR间的最佳切点.结果PD组血浆α-syn、p-α-syn、NfL水平均高于HC组,差异有统计学意义(Z=-2.537,-6.580,-7.101,均P<0.05).AR组与TD组病程、H-Y分期、UPDRS-Ⅲ评分、LEDD、MMSE 评分方面均差异有统计学意义(Z=-2.503,-3.021,-2.025,-2.086,-2.409,均P<0.05).AR组血浆α-syn、p-α-syn水平与TD组差异无统计学意义(Z=-0.341,-0.085,均 P>0.05),但 AR 组血浆 NfL 水平[92.79(16.84,117.53)pg/mL]显著高于 TD 组[12.10(6.99,100.17)pg/mL](Z=-2.236,P<0.05).血浆 NfL 水平与强直得分(r=0.438,P<0.001)、UPDRS-Ⅲ运动评分(r=0.337,P<0.05)和运动亚型(r=0.286,P<0.05)相关.多因素Logistic回归分析显示,NfL是 AR发生的独立影响因素(B=0.002,OR=1.002,95%CI=1.001~1.003,P=0.017).ROC曲线分析显示血浆NfL预测PD不同亚型的ROC曲线下面积为0.667,最佳截断值为26.527.结论 血浆NfL水平升高与PD患者AR的发生存在相关性,揭示了神经损伤可能参与了 PD不同运动亚型的发生和发展.
Correlation between plasma neurofilament light chain and subtypes of Parkinson disease
Objective To investigate the correlation between plasma total α-synuclein(α-syn),phosphorylated α-synuclein(p-α-syn),neurofilament light chain(NfL)and subtypes of Parkinson disease(PD).Methods A total of 62 PD patients admitted to the Department of Neurology,the Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University from September 2021 to January 2023 were selected and scored on the Hoehn-Yahr stage(H-Y),unified Parkinson's disease rating scale Ⅲ(UPDRS-Ⅲ),levo-dopa equivalent daily dosage(LEDD),mini-mental state examination(MMSE),Parkinson disease quality of life questionnaire(PDQ-39)and activities of daily living(ADL).During the same period,25 healthy indi-viduals matched in age and sex were enrolled as the control group(HC).Clinical characteristics and blood samples were collected.The plasma levels of α-syn,p-α-syn and NfL were detected by enzyme-linked immu-nosorbent assay(ELISA).PD patients were divided into tremor dominant type(TD,n=27)and akinetic-rig-id dominant type(AR,n=35)based on UPDRS-Ⅲ scores.Multifactorial Logistic regression analysis was performed by SPSS 25.0 software to determine the influencing factors of subtypes of Parkinson disease.The receiver operating characteristic(ROC)curve was used to determine the optimal cut-off point of plasma NfL between the AR type and the TD type.Results Plasma α-syn,p-α-syn,NfL levels in the PD group were significantly higher than those of the HC group(Z=-2.537,-6.580,-7.101,all P<0.05).There were sta-tistically significant differences between the AR type and the TD type in disease duration,H-Y stage,UPDRS-Ⅲ scores,LEDD and MMSE scores(Z=-2.503,-3.021,-2.025,-2.086,-2.409,all P<0.05).While no significant difference was found in plasma α-syn and p-α-syn levels between the AR type and TD type(Z=-0.341,-0.085,both P>0.05),the plasma NfL levels were notably higher in the AR type(92.79(16.84,117.53)pg/mL)compared to the TD type(12.10(6.99,100.17)pg/mL)(Z=-2.236,P<0.05).Plasma NfL levels were correlated with rigidity scores(r=0.438,P<0.001),UPDRS-Ⅲ scores(r=0.337,P<0.05)and motor subtypes(r=0.286,P<0.05)in PD patients.Multivariate Logistic regression a-nalysis showed that NfL was risk factor for AR(B=0.002,OR=1.002,95%CI=1.001-1.003,P=0.017).The ROC curve analysis indicated that plasma NfL levels could predict different subtypes of PD with an AUC=0.667,optimal cutoff=26.527.Conclusion There is a correlation between elevated plasma NfL levels and the occurrence of AR type of PD,suggesting that nerve injury is probably involved in the occurrence and progression of various motor subtypes of PD.

Parkinson diseaseNeurofilament light chainMotor subtypesα-synucleinCorrelation analysis

梁晓静、乙红艳、李天天、许富贵、王丽君、欧洲、佟强

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南京医科大学附属淮安第一医院神经内科,淮安 223300

帕金森病 神经丝蛋白轻链 运动亚型 α-突触核蛋白 相关分析

江苏省自然科学基金江苏省卫生健康委面上项目

BK20191212M2022082

2024

中华行为医学与脑科学杂志
中华医学会 济宁医学院

中华行为医学与脑科学杂志

CSTPCD北大核心
影响因子:1.472
ISSN:1674-6554
年,卷(期):2024.33(9)