血液生物标志物α突触核蛋白在帕金森病早期诊断中的应用

Abstract 2 3 2.1帕金森病的概述 42.2生物标志物的概述 5 7 8参考文献 9 10其中以α-突触核蛋白（α-synuclein，α-Syn）形成的路易小体为突出特征，其可在临床症状出现之前的数年甚至数十年内就已经存在REF_Ref25334\r\h[5]。帕金森病（Parkinson’sdisease，PD）早期诊断的一大难题就是缺乏特异性的生物标志物，以往PD的主要依据是运动症状，但到运动症状出现时，中脑黑质区的多巴胺能神经元丢失已经进行性严重REF_Ref25363\r\h[6]。近年来发现α-Syn是PD的核心病理蛋白，由于α-Syn在PD发病中的重要作用使其成为早期诊断PD的研究热点，因此有望在血液中检测到α-Syn从而实现PD早期甚至亚临床期的诊断。参考文献张亦弛,刘军.生物标志物助力帕金森病早期诊断[J],2023,43(10):812-821.DOI:10.19538/j.nk2023100105.BhangZX,GustavoCR,ChenH,etal.Parkinson'sdiseaseinChina:prevalenceinBeijing,Xian,andShanghai[J].Lancet,2005,365(9459):595-597.王红飞,白雪,张亚丽.帕金森病相关认知损害的生物学标志物研究进展[J].中国临床神经科学,2025,33(02):236-240.黄姝绮,李思琴,涂双燕,等.中国帕金森病患者抑郁情绪发生率的Meta分析[J].中风与神经疾病杂志,2020,37(11):984-988.BaianoC,BaroneP,TrojanoL,etal.PrevalenceandclinicalaspectsofmildcognitiveimpairmentinParkinson'sdisease:Ametaanalysis[J].MovDisord,2020,35(1):45-54.董文文,邱畅,章文斌.帕金森病血液生物标志物的研究进展[J].临床神经外科杂志,2020,17(01):113-115+120.MidiY,KanjiK,LoriF,etal.PLA2G6accumulatesinDewybodiesinPARK14andidiopathicParkinson’sdisease.Neuroscience.2017;645:40–45.do:10.1016/tle.2017.02.027.GuptaR,KimC,AgarN,etal.UnderstandingtheinfluenceofParkinsondiseaseonAdolfHitler’sdecision-makingduringWorldWarII.WorldNeuroses.2015;84:1447–1452.do:10.1016/j.neut.2015.06.014.CheriD,BliniM,CalT.Emerging(andconverging)pathwaysinParkinson’sdisease:keepingmitochondrialwellness.BiochemBiophysResCommun.2017;483:1020–1030.do:10.1016/j.abbr.2016.08.153.ChahineLM,SternMB,Chen-PlotkinA.Blood-basedbiomarkersforParkinson'sdisease.ParkinsonismRelatDisord.2014Jan;20Suppl1(01):S99-103.TöngesL,BuhmannC,KlebeS,etal.Blood-basedbiomarkerinParkinson'sdisease:potentialforfutureapplicationsinclinicalresearchandpractice.JNeuralTransm(Vienna).2022Sep;129(9):1201-1217.doi:10.1007/s00702-022-02498-1.Epub2022Apr15.PMID:35428925;PMCID:PMC9463345.HasegawaT,KobayashiJ,IshiyamaS.[EmergingDisease-modifying217StrategiesTargetingalpha-synucleininParkinson'sDisease][J].BrainNerve,2020,72(2):143-150.柳州,陈娟,张朝贵,等.帕金森病早期诊断及预后判断血液生物标志物研究进[J].神经损伤与功能重建,2025,20(04):215-219.DOI:10.16780/ki.sjssgncj.20250132.WilliamsSM,SchulzP,SierksMR.Oligomericalpha-synucleinandbeta-amyloidvariantsaspotentialbiomarkersforParkinson'sandAlzheimer’sdiseases[J].EurJNeurosci,2016,43(1):3-16.ChangCW,YangSY,YangCC,etal.PlasmaandSerumAlpha-SynucleinasaBiomarkerofDiagnosisinPatientsWithParkinson'sDisease[J].FrontNeurol,2019,10:1388.LinXM,CookTJ,ZabetianCP,etal.DJ-1isoformsinwholebloodaspotentialbiomarkersofParkinsondisease[J],SciRep,2012,2:954.AnnanmakiT,MuuronenA,MurrosK.LowplasmauricacidlevelinParkinson'sdisease[J].MovDisord,2007,22:1133.张瑜，樊开阳，张文利，等．血尿酸及其他血清学指标与帕金森病的相关性[J].中国老年学杂志,2017,37:2256.PanM,GaoH,LongL,etal.SerumuricacidinpatientswithParkinson'sdiseaseandvascularparkinsonism:across-sectionalstudy[J].Neuroimmunomodulation,2013,20:19.刘久江，钱逸维，徐绍卿，等.不同性别帕金森病患者血尿酸水平的相关性研究[J].临床神经病学杂志,2016,29:241.SenguptaU,KayedR.Amyloidbeta,Tau,andalpha-Synucleinaggregatesinthepathogenesis,prognosis,andtherapeuticsforneurodegenerativediseases[J].ProgNeurobiol,2022,214:102270.ZhangS,ZhuR,PanB,etal.Post-translationalmodificationsofsolublealpha-synucleinregulatetheamplificationofpathologicalalpha-synuclein[J].NatNeurosci,2023,26(2):213-225.ForloniG.AlphaSynuclein:NeurodegenerationandInflammation[J].IntJMolSci,2023,24(6):5914.StefanisL.alpha-SynucleininParkinson'sdisease[J].ColdSpringHarbPerspectMed,2012,2(2):a9399.谢振华.帕金森病标志物磷酸化α-突触核蛋白在血浆外泌体中的定量分析研究[D].郑州大学,2019.BarbourR,KlingK,AndersonJP,etal.Redbloodcellsarethemajorsourceofalphα-synucleininblood.NeurodegenerDis.2008;5(2):55–59.doi:10.1159/000112832.LinC-H,YangS-Y,HorngH-E,etal.Plasmaα-synucleinpredictscognitivedeclineinParkinson'sdisease.JNeurolNeurosurgPsychiatry.2017;88(10):818–824.doi:10.1136/jnnp-2016-314857.MataIF,ShiM,AgarwalP,etal.SNCAvariantassociatedwithParkinsondiseaseandplasmaalphα-synucleinlevel.ArchNeurol.2010;67(11):1350–1356.doi:10.1001/archneurol.2010.279.Besong-AgboD,WolfE,JessenF,OechsnerM,etal.Naturallyoccurringα-synucleinautoantibodylevelsarelowerinpatientswithParkinsondisease.Neurology.2013;80(2):169–175.doi:10.1212/WNL.El-AgnafOMA,SalemSA,PaleologouKE,etal.Detectionofoligomericformsofalphα-synucleinproteininhumanplasmaasapotentialbiomarkerforParkinson'sdisease.FASEBj:offPublFederationAmSocExpBiol.2006;20(3):419–425.doi:10.1096/fj.03-1449com.DanieleS,FrosiniD,PietrobonoD,etal.α-Synucleinheterocomplexeswithβ-AmyloidareincreasedinredbloodcellsofParkinson'sdiseasepatientsandcorrelatewithdiseaseseverity.FrontMolNeurosci.2018;11:53.doi:10.3389/fnmol.2018.00053.何倩.帕金森病患者皮肤神经中磷酸化α-突触核蛋白研究[D].郑州大学,2020.DOI:10.27466/ki.gzzdu.2020.003139.AbdElhadiS,GrigolettoJ,PoliM,etal.α-SynucleininbloodcellsdifferentiatesParkinson’sdiseasefromhealthycontrols.AnnClinTranslNeurol.2019;6(12):2426–2436.doi:10.1002/acn3.50944.WangX，YuS，LiF，etal.Detectionofα-s