2024
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
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, 1-11. 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
The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J
Toyonaga T, Khattar N, Wu Y, Lu Y, Naganawa M, Gallezot J, Matuskey D, Mecca A, Pittman B, Dias M, Nabulsi N, Finnema S, Chen M, Arnsten A, Radhakrishnan R, Skosnik P, D’Souza D, Esterlis I, Huang Y, van Dyck C, Carson R. The regional pattern of age-related synaptic loss in the human brain differs from gray matter volume loss: in vivo PET measurement with [11C]UCB-J. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 51: 1012-1022. PMID: 37955791, DOI: 10.1007/s00259-023-06487-8.Peer-Reviewed Original ResearchSynaptic densityAge-related decreaseMagnetic resonance imagingBlood flowAge-related synaptic lossGray matter volume lossSynaptic density lossPositron emission tomography (PET) ligandSynaptic vesicle glycoprotein 2AVivo PET measurementsMedial occipital cortexGray matter volumeAge-related neurodegenerationGray matter regionsCognitive normal subjectsAge-related changesSynaptic lossNerve terminalsWide age rangeOccipital cortexTomography ligandNormal subjectsGM volumeAge-related functional lossesMatter volumeAssessment 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 impairmentDiseaseIn 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
2020
PET Imaging of Synaptic Vesicle Protein 2A
Finnema S, Li S, Cai Z, Naganawa M, Chen M, Matuskey D, Nabulsi N, Esterlis I, Holmes S, Radhakrishnan R, Toyonaga T, Huang Y, Carson R. PET Imaging of Synaptic Vesicle Protein 2A. 2020, 993-1019. DOI: 10.1007/978-3-030-53176-8_29.ChaptersSynaptic vesicle protein 2APositron emission tomographyAntiepileptic drug levetiracetamInitial PET studiesPET imagingPET studiesSynaptic densityDrug levetiracetamHigh-affinity SV2A ligandsBrain regionsSynaptic density lossNeuropathological diseasesDisease-modifying therapiesLarge patient cohortMajor depressive disorderProtein 2APET imaging resultsPosttraumatic stress disorderPatient groupPatient cohortDepressive disorderClinical valueParkinson's diseaseEfficacy assessmentSynaptic vesicle proteins