腦淀粉樣血管病-趙元立（英文）

CerebralAmyloidAngiopathy

腦淀粉樣血管病趙元立北京天壇醫(yī)院WhatisCAA?amyloiddepositionaged(>=50-60y)arteriesofthecortical,subcorticalareasM&FinincidenceRecurrent,MultipleHemorrhagePradaetal.,J.Neurosci.,2007BackgroundCerebralamyloidangiopathy(CAA)-depositionofβ-amyloidinthemediaandadventitiaofsmall-andmid-sizedarteriesICH-mostrecognizedresultof

CAARelationwithAlzheimerdiseaseCerebralAmyloidangiopathy

Two-photonprojectionofaz-seriesabout150umdeepintothebrainofaliving20-mo-oldtransgenicmouseexpressingamutanthumanamyloidprecursorprotein.Thisanimalhadamyloiddepositssurroundingsomecerebralvessels.

BrianJ.Bacskai,MassachusettsGeneralHospital,USA

EpidemiologyUnitedStates~upto15%ofallICH>60upto50%ofnontraumaticlobarICH>70~15-20per100,000population/yearaseriesof400autopsies:CAAin18.3%ofmen28%ofwomen(age40-90)aseriesof117confirmedAD:83%CAAGreenbergSM,Stroke

28(7):1418–22July1997SexandAgeSexmaybemorecommonlyinwomenincidenceofICHissameAgeagerelatedSporadicICHoccurs>60FamilialCAAatyoungeragesIcelandicform30-40,Dutch50-60DiagnosisCCheadache,vomiting,hemiplegia…PHwithouthypertension,asymptomaticPEICHrelatedfindingsCT/MRIlobar/cortical/subcorticalSAH,ventricularhemorrhage

梯度回聲MR:sensitivetomicrohemorrhagePathologyCongoRed(+),Aβ(+)TransaxialT2-weightedgradient-echoMRimagesshowinnumerablemicrohemorrhagespredominantlyatcerebralgray–whitematterjunction.Microhemorrhagesarenotpresentinbasalganglia,pons,orcerebellum.LargefocalhemorrhagesarepresentinbilateralparietallobeMarisaKastoffBlitsteinAJR2007;189:720-725

GuidelinefordiagnosisBostonGroup-FourlevelsDefiniteCAA:lobar,cortical,orsubcorticalhemorrhageevidenceofsevereCAAProbableCAAwithsupportingpathologicalevidence:clinicaldata+somedegreeofvascularamyloiddepositionProbableCAA:clinicaldata+MR,nopathologicalspecimenmultiplehematomasinpatient>60PossibleCAA:patient>60clinical+MR:singlelobar,cortical,orcorticosubcorticalhemorrhage,noothercausemultiplehemorrhageswithapossiblebutnotadefinitecauseorsomehemorrhageinanatypicallocationKnudsenKA,Neurology2001;56:537–9.BhomrajThanviAgeandAgeing200635(6):565-571SpecialtypeofCAADutchtypeofhereditarycerebralhemorrhage:autosomaldominant,withmutationofamyloidprecursorprotein,atage40–60,mayproduceanabnormalanti-coagulant,whichmakeshemorrhagemorelikely.FamilialAlzheimer'sdisease:autosomaldominant,5–10%ofallADIcelandictype:autosomaldominant,withmutationinthegenecodingforcystatinC,beginat30–40withmultiplebrainhemorrhages,mostinvolvethebasalgangliaDownSyndrome:trisomy21Britishtypeoffamilialamyloidosis:autosomaldominant,associatedwithprogressivedementia,spasticity,andataxia.Brainstem,spinalcord,andcerebellumallexhibitamyloiddeposits,buthemorrhagetypicallydoesnotoccur.WhybleedingBleedingintobrainoccurastinybloodvesselscarryingamyloiddepositsbecomeheavierandmorebrittlemorelikelytoburstwithminortraumaorwithfluctuatingbloodpressureAneurysmsmaydevelop,andmayalsoruptureAmyloiddepositsmaydestroysmoothmusclecellsorcauseinflammationinthebloodvesselwall,causebloodvesseltobreakmoreeasilySethLove,FrontiersinBioscience14,4778-4792,January,2009ThecauseofamyloiddepositsinbloodvesselsinthebraininsporadicCAAisnotknownInhereditaryCAA,geneticdefects,typicallyonchromosome21,allowaccumulationofamyloid,aproteinmadeupofunitscalledbeta-pleatedsheetfibrils.Thefibrilstendtoclumptogether,sothattheamyloidcannotbedissolvedandbuildsupinthebrainbloodvesselwalls.Oneformofamyloidfibrilsubunitproteinsistheamyloidbetaprotein.StevenGreenbergGeriatricsandaging,200811(5):15-17Systemictheoryamyloidbetaproteininblooddepositedinbloodvesselsinthebrainbreakdownblood-brainbarrieramyloidbetaproteindepositedinbrainsubstanceformsneuriticplaqueSecondtheoryamyloidfibrilsproducedbyperivascularmicrogliaThirdtheorybothnervecellsandgliaproduceamyloidprecursorprotein,increaseswithaging病理機制AmyloiddamagesthemediaandadventitialeadingtothickeningofthebasalmembranestenosisofthevessellumenfragmentationoftheinternalelasticlaminaresultinfibrinoidnecrosisandmicroaneurysmformationSomeevidencesuggeststhattheamyloidisproducedinthesmoothmusclecellsofthetunicamediaasaresponsetodamageofthevesselwall(perhapsbyarteriosclerosisorhypertension)病理機制severalkeyprocessesareinvolved:productionofamyloidprecursorproteins(APP),processingofprecursorproteins,aggregationofprotein,andfibrilformation.

Impairedeliminationandaccumulationofsolubleandinsolubleβ-amyloidpeptidemayunderliethepathogenesisofCAAandexplainthelinkbetweenCAAandAD.ElectronmicroscopydemonstratesfibrilsofamyloidintheouterbasementmembraneintheinitialstageofCAAManytypesofamyloidproteinarepresentinthebody,butsomeareuniquetothebrain.β-amyloidisauniquecerebrovascularamyloidproteinAmyloidFamily:AβACysATTRAGelPrPScABriADan病理特點受累血管壁常規(guī)染色在光鏡下呈不成形的，強嗜伊紅的玻璃樣即淀粉樣改變剛果紅染色呈粉紅陽性物質(zhì)在血管及其周圍沉積，即嗜剛果紅血管病腦膜及皮質(zhì)中、小血管受累淀粉樣物質(zhì)多沉積于血管中膜及外膜血管壁增厚，管腔狹窄腦淀粉樣血管病腦膜表面大血管硬化，管腔狹窄附近小動脈亦明顯變性x50腦實質(zhì)內(nèi)可見大量淀粉樣小體形成腦實質(zhì)小血管管壁增厚、變性中等量淀粉樣小體形成x100HEVSCongoRedPathology由皮層向皮層下過度的區(qū)域中受累血管的分布情況高倍鏡下典型的嗜剛果紅染色的血管壁，呈現(xiàn)“雙環(huán)”狀標本中可見不同程度受累的血管由低倍到高倍示Aβ(+)的腦血管，集中分布在皮層及皮層下區(qū)域gradingMortality