2024
Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at 18F-SynVesT-1 Brain PET Imaging.
Wu J, Li B, Wang J, Huang Q, Chen X, You Z, He K, Guo Q, Li S, Huang Y, Guo T, Dai W, Xiang W, Chen W, Yang D, Zhao J, Guan Y, Xie F, Wolfe S. Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at 18F-SynVesT-1 Brain PET Imaging. Radiology 2024, 313: e233019. PMID: 39560478, PMCID: PMC11605102, DOI: 10.1148/radiol.233019.Peer-Reviewed Original ResearchConceptsP-tau-181Alzheimer's diseaseAD-related pathologyAmyloid-bPhosphor-tauTau pathologySynaptic densityTau accumulationSynaptic lossTauTau-PETDecreased synaptic densityGlial fibrillary acidic proteinPlasma glial fibrillary acidic proteinCortical thicknessAcidic proteinFibrillary acidic proteinRuijin HospitalProspective studyRelationship of plasmaBlood assayBlood markersPET/MRIBrain PET imagingPET imagingValidation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET
Young J, O’Dell R, Naganawa M, Toyonaga T, Chen M, Nabulsi N, Huang Y, Cooper E, Miller A, Lam J, Bates K, Ruan A, Nelsen K, Salardini E, Carson R, van Dyck C, Mecca A. Validation of a Simplified Tissue-to-Reference Ratio Measurement Using SUVR to Assess Synaptic Density Alterations in Alzheimer Disease with [11C]UCB-J PET. Journal Of Nuclear Medicine 2024, 65: jnumed.124.267419. PMID: 39299782, PMCID: PMC11533916, DOI: 10.2967/jnumed.124.267419.Peer-Reviewed Original ResearchDistribution volume ratioSUV ratioSynaptic densityEffect sizeAlzheimer's diseaseLongitudinal study of Alzheimer's diseaseMethods:</b> ParticipantsLongitudinal studyMeasure synaptic densityAD participantsStudy of Alzheimer's diseaseNormal cognitionReference regionOlder adultsMulticenterDensity alterationsLoss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study
Li B, Chen H, Zheng Y, Xu X, You Z, Huang Q, Huang Y, Guan Y, Zhao J, Liu J, Xie F, Wang J, Xu W, Zhang J, Deng Y. Loss of synaptic density in nucleus basalis of meynert indicates distinct neurodegeneration in Alzheimer’s disease: the RJNB-D study. European Journal Of Nuclear Medicine And Molecular Imaging 2024, 1-11. PMID: 39112615, DOI: 10.1007/s00259-024-06862-z.Peer-Reviewed Original ResearchWhite matter tractsCognitive impairmentSynaptic densityCognitive performancePositron emission tomographyNucleus basalisSeverity of cognitive impairmentAlzheimer's diseaseSynaptic lossNucleus basalis of MeynertBasalis of MeynertSynaptic vesicle glycoprotein 2Pathogenesis of Alzheimer's diseaseStandardized uptake value ratioCholinergic systemProfile of ADCN participantsPotential impairmentMMSE scoreMedial tractNBMImpairmentEmission tomographyLoss of synaptic densityNormal controlsPresynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment
Wang J, Huang Q, He K, Li J, Guo T, Yang Y, Lin Z, Li S, Vanderlinden G, Huang Y, Van Laere K, Guan Y, Guo Q, Ni R, Li B, Xie F. Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment. Alzheimer's & Dementia 2024, 20: 3876-3888. PMID: 38634334, PMCID: PMC11180932, DOI: 10.1002/alz.13817.Peer-Reviewed Original ResearchMGluR5 availabilityMedial temporal lobeSynaptic densityTemporal lobeHealthy controlsAlzheimer's diseaseMetabotropic glutamate receptor 5Glutamate receptor 5Synaptic lossIntegrative brain functionsCognitively impaired patientsEarly cognitive impairmentGlobal cognitionMGluR5 signalingMediation analysisPathophysiological mechanism of Alzheimer's diseaseBrain functionCognitive impairmentMGluR5CognitionImproving synaptic functionImpaired patientsSynaptic functionSynaptic transmissionAmyloid pathologyTau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer’s disease
Wang J, Huang Q, Chen X, You Z, He K, Guo Q, Huang Y, Yang Y, Lin Z, Guo T, Zhao J, Guan Y, Li B, Xie F. Tau pathology is associated with synaptic density and longitudinal synaptic loss in Alzheimer’s disease. Molecular Psychiatry 2024, 29: 2799-2809. PMID: 38589563, DOI: 10.1038/s41380-024-02501-z.Peer-Reviewed Original ResearchTau pathologySynaptic lossTau tanglesAlzheimer's diseaseAssociated with synaptic lossAD patientsMild cognitive impairmentMild cognitive impairment patientsAmyloid-bPlasma p-tauP-tau181 levelsAssociation of ABSynaptic densityP-tauNormal controlsPositron emission tomographyMediation analysisTemporal lobeTauTau burdenP-tau181One-year follow-up assessmentSeventy-five participantsTanglesFollow-up assessmentAPOE ε4 is associated with decreased synaptic density in cognitively impaired participants
He K, Li B, Wang J, Wang Y, You Z, Chen X, Chen H, Li J, Huang Q, Guo Q, Huang Y, Guan Y, Chen K, Zhao J, Deng Y, Xie F. APOE ε4 is associated with decreased synaptic density in cognitively impaired participants. Alzheimer's & Dementia 2024, 20: 3157-3166. PMID: 38477490, PMCID: PMC11095422, DOI: 10.1002/alz.13775.Peer-Reviewed Original ResearchApolipoprotein E4Tau pathologyAlzheimer's diseaseApo E4AD biomarkersAPOE e4 allele carriersAmyloid-betaEffects of apolipoprotein E4Synaptic lossAPOE e4 alleleSynaptic densitySynaptic density lossNon-carriersE4 alleleE4 allele carriersE4 genotypeTauGenotypesPositron emission tomographyAllele carriersMedial temporal lobeAllelesAmyloidEffect of APOE E4Cognitively impaired participantsThe associations between synaptic density and “A/T/N” biomarkers in Alzheimer’s disease: An 18F-SynVesT-1 PET/MR study
Li J, Huang Q, Qi N, He K, Li S, Huang L, Pan F, Ren S, Hua F, Huang Y, Guan Y, Guo Q, Zhao J, Xie F. The associations between synaptic density and “A/T/N” biomarkers in Alzheimer’s disease: An 18F-SynVesT-1 PET/MR study. Cerebrovascular And Brain Metabolism Reviews 2024, 44: 1199-1207. PMID: 38295871, PMCID: PMC11179616, DOI: 10.1177/0271678x241230733.Peer-Reviewed Original ResearchSynaptic densityF-FDG PET/CTInvestigate synaptic densityFDG uptakeF-FDGCognitive impairmentClinical syndromeCI groupPlasma testingPET/MR studiesPathological changesSubgroups of individualsSynaptic density lossDensity lossBiomarkersAlzheimer's clinical syndromePatientsPET/MRHippocampusAlzheimer's diseaseHippocampal volumeParahippocampal gyrusCI+ groupDiseaseSynapse lossA pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease
van Dyck C, Mecca A, O’Dell R, Bartlett H, Diepenbrock N, Huang Y, Hamby M, Grundman M, Catalano S, Caggiano A, Carson R. A pilot study to evaluate the effect of CT1812 treatment on synaptic density and other biomarkers in Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 20. PMID: 38273408, PMCID: PMC10809445, DOI: 10.1186/s13195-024-01382-2.Peer-Reviewed Original ResearchConceptsMild to moderate dementiaPositron emission tomographyAlzheimer's diseaseVolumetric MRIModerate dementiaClinical rating scalesSynaptic vesicle glycoprotein 2ACerebrospinal fluidMouse model of ADPharmacodynamic effectsPlacebo-controlled phase 1 clinical trialBiomarkers of AD pathologyClinical trialsCognitive measuresNominally significant differencesPhase 1 clinical trialModel of ADHippocampal cortexPhase 1/2 studyRating ScaleParallel-group trialSynaptic densityTrial registrationThe clinical trialPlacebo-controlledSigma-2 receptor ligands
2023
PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease
Zheng C, Nicholson L, Chen B, Toyonaga T, Liu M, Strittmatter S, Carson R, Huang Y, Cai Z. PET Imaging of Rho‐Associated Protein Kinase 2 in A Mouse Model of Alzheimer’s Disease. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.081695.Peer-Reviewed Original ResearchAPP/PS1 micePS1 miceWT miceCentral nervous systemTime-activity curvesAlzheimer's diseaseAPP/PS1 transgenic miceAPP/PS1 transgenic AD miceMouse brainAge-matched WT controlsPS1 transgenic miceAPP/PS1Transgenic AD miceDynamic PET imaging dataROCK2 protein expressionAD drug discoveryHigh tracer uptakeMin post injectionPET imaging resultsExpression levelsReference tissue model 2PET imaging dataProtein expression levelsAD miceRegional time-activity curvesEvaluation of a First PET Tracer Suitable for Imaging the Sigma‑2 Receptor in the Brain of Nonhuman Primates
Alluri S, Zheng M, Holden D, Zhang Y, Zhang L, Felchner Z, Li S, Ropchan J, Carson R, Jia H, Huang Y. Evaluation of a First PET Tracer Suitable for Imaging the Sigma‑2 Receptor in the Brain of Nonhuman Primates. Molecular Pharmaceutics 2023, 21: 194-200. PMID: 38013422, DOI: 10.1021/acs.molpharmaceut.3c00750.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseLimited brain uptakeNonhuman primate brainCentral nervous systemPotential therapeutic targetPositron emission tomography (PET) imagingEmission Tomography ImagingTransmembrane protein 97Sigma-2 receptorsFirst PET tracerBrain penetrantBrain uptakeTherapeutic targetNervous systemPrimate brainNeurological disordersPET tracersNonhuman primatesTomography imagingProtein 97CancerDiseaseBrainCell typesReceptorsAssessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET
Silva-Rudberg J, Salardini E, O'Dell R, Chen M, Ra J, Georgelos J, Morehouse M, Melino K, Varma P, Toyonaga T, Nabulsi N, Huang Y, Carson R, van Dyck C, Mecca A. Assessment of Gray Matter Microstructure and Synaptic Density in Alzheimer's Disease: A Multimodal Imaging Study With DTI and SV2A PET. American Journal Of Geriatric Psychiatry 2023, 32: 17-28. PMID: 37673749, PMCID: PMC10840732, DOI: 10.1016/j.jagp.2023.08.002.Peer-Reviewed Original ResearchSynaptic densityAlzheimer's diseaseMean diffusivitySynaptic lossGray matter microstructureGray matter mean diffusivityDisease pathologyHippocampal synaptic densityMajor pathological correlateSetting of ADAD-related neuropathologySynaptic vesicle glycoprotein 2AHippocampal mean diffusivityAlzheimer's disease pathologyAmyloid-positive participantsMatter mean diffusivityPositron emission tomography (PET) imagingEmission Tomography ImagingGray matter structuresPathological correlatesPositive participantsInverse associationAD groupCognitive impairmentDiseasePrincipal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease
O'Dell R, Higgins-Chen A, Gupta D, Chen M, Naganawa M, Toyonaga T, Lu Y, Ni G, Chupak A, Zhao W, Salardini E, Nabulsi N, Huang Y, Arnsten A, Carson R, van Dyck C, Mecca A. Principal component analysis of synaptic density measured with [11C]UCB-J PET in early Alzheimer’s disease. NeuroImage Clinical 2023, 39: 103457. PMID: 37422964, PMCID: PMC10338149, DOI: 10.1016/j.nicl.2023.103457.Peer-Reviewed Original ResearchConceptsCognitive domainsCognitive performanceSubjects' scoresCortical regionsNeuropsychological batteryEarly Alzheimer's diseaseAD groupBilateral regionsNormal participantsNegative loadingsCognitive impairmentCN participantsAlzheimer's diseaseParticipantsStructural correlatesStrong contributionParticipant characteristicsScoresPositive loadingsData-driven approachTotal variancePrincipal component analysisSpecific spatial patternsDecreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16
Zheng C, Toyonaga T, Chen B, Nicholson L, Mennie W, Liu M, Spurrier J, Deluca K, Strittmatter S, Carson R, Huang Y, Cai Z. Decreased synaptic vesicle glycoprotein 2A binding in a rodent model of familial Alzheimer's disease detected by [18F]SDM-16. Frontiers In Neurology 2023, 14: 1045644. PMID: 36846134, PMCID: PMC9945093, DOI: 10.3389/fneur.2023.1045644.Peer-Reviewed Original ResearchStandardized uptake value ratioDistribution volume ratioAlzheimer's diseaseSimplified reference tissue modelSynapse lossMouse modelAPP/PS1 miceAge-matched wild-type miceAPPswe/PS1dE9 mouse modelAPP/PS1 AD mouse modelSlow brain kineticsAD mouse modelSynaptic vesicle glycoprotein 2APseudo-reference regionWild-type miceUptake value ratioMonths of ageDifferent brain regionsDifferent imaging windowsFamilial Alzheimer's diseasePET imaging studiesReference tissue modelPS1 miceBrain stemBrain kineticsInvestigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans
Sawant‐Basak A, Chen L, Lockwood P, Boyden T, Doran A, Mancuso J, Zasadny K, McCarthy T, Morris E, Carson R, Esterlis I, Huang Y, Nabulsi N, Planeta B, Fullerton T. Investigating CNS distribution of PF‐05212377, a P‐glycoprotein substrate, by translation of 5‐HT6 receptor occupancy from non‐human primates to humans. Biopharmaceutics & Drug Disposition 2023, 44: 48-59. PMID: 36825693, DOI: 10.1002/bdd.2351.Peer-Reviewed Original ResearchConceptsNon-human primatesBrain penetrationPositron emission tomographyReceptor occupancyUnbound concentrationsPre-clinical evidenceVivo brain penetrationConcentration-dependent increaseP-glycoprotein substratesPlasma ECsP-gpAlzheimer's diseaseEmission tomographyRat BBBTarget engagementCumulative evidenceDependent increaseTransporter substratesCNS distributionBBBRatsDiseasePrimatesSpecies differencesHumansIn vivo synaptic density loss correlates with impaired functional and related structural connectivity in Alzheimer’s disease
Zhang J, Wang J, Xu X, You Z, Huang Q, Huang Y, Guo Q, Guan Y, Zhao J, Liu J, Xu W, Deng Y, Xie F, Li B. In vivo synaptic density loss correlates with impaired functional and related structural connectivity in Alzheimer’s disease. Cerebrovascular And Brain Metabolism Reviews 2023, 43: 977-988. PMID: 36718002, PMCID: PMC10196742, DOI: 10.1177/0271678x231153730.Peer-Reviewed Original ResearchConceptsMiddle frontal gyrusAlzheimer's diseaseSynaptic densityMild cognitive impairmentSynapse lossCognitive impairmentCaudal middle frontal gyrusFunctional connectivityLower synaptic densityMajor pathological changesRight insular cortexStructural connectivity alterationsRight middle frontal gyrusWhite matter tractsSynaptic alterationsBilateral cortexConnectivity alterationsInsular cortexAD groupPathological changesConnectivity dysfunctionCognitive declineCognitive functionFunctional MRIDisease
2021
Chapter 15 Positron emission tomography imaging agents for evaluating the pathologic features of Alzheimer's disease and drug development
Huang Y, Jia H, Bao W. Chapter 15 Positron emission tomography imaging agents for evaluating the pathologic features of Alzheimer's disease and drug development. 2021, 367-412. DOI: 10.1016/b978-0-12-816475-4.00013-6.Peer-Reviewed Original ResearchAlzheimer's diseasePathologic featuresApplication of PETDrug developmentSynaptic vesicle protein 2ADifferent pathologic featuresFeatures of neurodegenerationCentral nervous systemAD drug developmentPositron emission tomographyNeuroinflammation biomarkersCholinergic systemΒ-amyloidNervous systemTau proteinEmission tomographyAD researchDiseaseProtein 2AInvestigation of diseasesQuantitative imaging techniquesTomographyImaging techniquesAgentsPET
1998
Chapter 44 Characterization of the Radiolabeled Metabolites of [18F]Altanserin Implications for Kinetic Modeling
Lopresti B, Holt D, Mason N, Huang Y, Ruszkiewicz J, Perevuznik J, Price J, Smith G, Davis J, Mathis C. Chapter 44 Characterization of the Radiolabeled Metabolites of [18F]Altanserin Implications for Kinetic Modeling. 1998, 293-298. DOI: 10.1016/b978-012161340-2/50046-9.Peer-Reviewed Original ResearchVivo positron emission tomography (PET) imaging studiesPositron emission tomography (PET) imaging studiesTomography Imaging StudyPostmortem brain studiesSerotonergic abnormalitiesSerotonergic dysfunctionMajor depressionRadiolabeled metabolitesTherapeutic efficacyAlzheimer's diseaseImaging studiesNeurodegenerative disordersPET studiesReceptorsBrain studiesVivo propertiesDiseaseRadioligandDisordersDysfunctionAltanserinAbnormalitiesNonspecific bindingSchizophrenia