Resting-State Network Disruption and APOE Genotype in Alzheimers Disease A lagged Functional Connectivity Study 英文参考文献.docVIP

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Resting-State Network Disruption and APOE Genotype in Alzheimers Disease A lagged Functional Connectivity Study 英文参考文献.doc

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Resting-State Network Disruption and APOE Genotype in Alzheimers Disease A lagged Functional Connectivity Study 英文参考文献

Resting-StateNetworkDisruptionandAPOEGenotypein Alzheimer’sDisease:AlaggedFunctionalConnectivity Study LeonidesCanuet1*,IvanTellado1,VeronicaCouceiro1,CarmenFraile1,LuciaFernandez-Novoa2, RyouheiIshii3,MasatoshiTakeda3,RamonCacabelos1,2 1EuroEspesBiomedicalResearchCenter,InstituteforCNSDisordersandGenomicMedicine,Corunna,Spain,2EuroEspesBiotechnologyDivision(Ebiotec),Institutefor CNSDisordersandGenomicMedicine,Corunna,Spain,3DepartmentofPsychiatry,OsakaUniversityGraduateSchoolofMedicine,Suitacity,Osaka,Japan Abstract Background:TheapolipoproteinEepsilon4(APOE-4)isassociatedwithageneticvulnerabilitytoAlzheimer’sdisease(AD) andwithAD-relatedabnormalitiesincorticalrhythms.However,itisunclearwhetherAPOE-4islinkedtoaspecificpattern ofintrinsicfunctionaldisintegrationofthebrainafterthedevelopmentofthediseaseorduringitsdifferentstages.This study aimed at identifying spatial patterns and effects of APOE genotype on resting-state oscillations and functional connectivityinpatientswithAD,usingaphysiologicalconnectivityindexcalled‘‘laggedphasesynchronization’’. Methodology/PrincipalFindings:RestingEEGwasrecordedduringawake,eyes-closedstatein125patientswithADand 60elderlycontrols.SourcecurrentdensityandfunctionalconnectivityweredeterminedusingeLORETA.PatientswithAD exhibited reduced parieto-occipital alpha oscillations compared with controls, and those carrying the APOE-4 allele had reducedalphaactivityintheleftinferiorparietalandtemporo-occipitalcortexrelativetononcarriers.Therewasadecreased alpha2connectivitypatterninAD,involvingthelefttemporalandbilateralparietalcortex.Severalbrainregionsexhibited increasedlaggedphasesynchronizationinlowfrequencies,specificallyinthethetaband,acrossandwithinhemispheres, wheretemporallobeconnectionswereparticularlycompromised.Areaswithabnormalthetaconnectivitycorrelatedwith cognitivescores.InpatientswithearlyAD,wefoundanAPOE-4-relateddecreaseininterhemisphericalphaconnectivityin frontalandparieto-temporalregions. Conclusions/Significance:Inad