2023
Principal 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 ResearchMeSH KeywordsAlzheimer DiseaseAmyloidAmyloidogenic ProteinsBrainCognitive DysfunctionHumansPositron-Emission TomographyPrincipal Component AnalysisConceptsCognitive 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 patterns
2022
Imaging of Synaptic Density in Neurodegenerative Disorders
Carson RE, Naganawa M, Toyonaga T, Koohsari S, Yang Y, Chen MK, Matuskey D, Finnema SJ. Imaging of Synaptic Density in Neurodegenerative Disorders. Journal Of Nuclear Medicine 2022, 63: 60s-67s. PMID: 35649655, DOI: 10.2967/jnumed.121.263201.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAnimalsHumansMembrane GlycoproteinsMiceNerve Tissue ProteinsPositron-Emission TomographyRadiopharmaceuticalsRatsConceptsSynaptic densityAlzheimer's diseaseNeurodegenerative disordersNeurodegenerative diseasesSynaptic vesicle protein 2APotential reference regionsSynaptic density lossLewy body dementiaProgressive supranuclear palsyDisease-modifying therapiesSpecific brain proteinsLarge patient cohortAntiepileptic drug levetiracetamPET imaging resultsMultiple neurodegenerative disordersSynaptic lossSupranuclear palsyCorticobasal degenerationNeuropathologic diseasePatient cohortRat modelClinical valueF-FDGParkinson's diseaseEfficacy assessmentSynaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB‐J
Mecca AP, O'Dell RS, Sharp ES, Banks ER, Bartlett HH, Zhao W, Lipior S, Diepenbrock NG, Chen M, Naganawa M, Toyonaga T, Nabulsi NB, Vander Wyk B, Arnsten AFT, Huang Y, Carson RE, van Dyck C. Synaptic density and cognitive performance in Alzheimer's disease: A PET imaging study with [11C]UCB‐J. Alzheimer's & Dementia 2022, 18: 2527-2536. PMID: 35174954, PMCID: PMC9381645, DOI: 10.1002/alz.12582.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseBrainCognitionCognitive DysfunctionHumansPositron-Emission TomographySynapsesConceptsSynaptic densityEarly Alzheimer's diseaseAlzheimer's diseaseCognitive performanceMajor pathological correlateGray matter volumePositron emission tomography (PET) imagingEmission Tomography ImagingPET imaging studiesIndividual cognitive domainsNeuropathologic studiesSignificant positive associationSynapse lossSynaptic alterationsPathological correlatesNeuropsychological test performanceMatter volumeCognitive impairmentSignificant associationImaging studiesDiseaseTomography imagingGlobal cognitionStrongest predictorPositive association
2021
Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease
Mecca AP, Chen MK, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Banks ER, Ni GS, Rogers K, Gallezot JD, Ropchan J, Emery PR, Nabulsi NB, Vander Wyk BC, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Association of entorhinal cortical tau deposition and hippocampal synaptic density in older individuals with normal cognition and early Alzheimer's disease. Neurobiology Of Aging 2021, 111: 44-53. PMID: 34963063, PMCID: PMC8761170, DOI: 10.1016/j.neurobiolaging.2021.11.004.Peer-Reviewed Original ResearchMeSH KeywordsAgingAlzheimer DiseaseCognitionEntorhinal CortexHealthy AgingHippocampusSynapsesTau ProteinsConceptsHippocampal synaptic densitySynaptic densityAlzheimer's diseaseCortical tau depositionEarly neuropathologic changesInitial clinical featuresSynaptic vesicle glycoprotein 2AEarly Alzheimer's diseaseOverall sampleEntorhinal cortical cellsClinical featuresNeuropathologic changesTau depositionTau pathologyInverse associationPerforant pathAD groupSynaptic failureNormal cognitionOlder individualsEarly degenerationDiseaseNormal participantsHippocampusTauGeneration of synthetic PET images of synaptic density and amyloid from 18F‐FDG images using deep learning
Wang R, Liu H, Toyonaga T, Shi L, Wu J, Onofrey JA, Tsai Y, Naganawa M, Ma T, Liu Y, Chen M, Mecca AP, O’Dell R, van Dyck C, Carson RE, Liu C. Generation of synthetic PET images of synaptic density and amyloid from 18F‐FDG images using deep learning. Medical Physics 2021, 48: 5115-5129. PMID: 34224153, PMCID: PMC8455448, DOI: 10.1002/mp.15073.Peer-Reviewed Original ResearchPartial volume correction analysis for 11C-UCB-J PET studies of Alzheimer's disease
Lu Y, Toyonaga T, Naganawa M, Gallezot JD, Chen MK, Mecca AP, van Dyck CH, Carson RE. Partial volume correction analysis for 11C-UCB-J PET studies of Alzheimer's disease. NeuroImage 2021, 238: 118248. PMID: 34119639, PMCID: PMC8454285, DOI: 10.1016/j.neuroimage.2021.118248.Peer-Reviewed Original ResearchComparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study
Chen MK, Mecca AP, Naganawa M, Gallezot JD, Toyonaga T, Mondal J, Finnema SJ, Lin SF, O’Dell R, McDonald JW, Michalak HR, Vander Wyk B, Nabulsi NB, Huang Y, Arnsten AF, van Dyck CH, Carson RE. Comparison of [11C]UCB-J and [18F]FDG PET in Alzheimer’s disease: A tracer kinetic modeling study. Cerebrovascular And Brain Metabolism Reviews 2021, 41: 2395-2409. PMID: 33757318, PMCID: PMC8393289, DOI: 10.1177/0271678x211004312.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseFemaleFluorodeoxyglucose F18HumansMaleMiddle AgedPositron-Emission TomographyConceptsSynaptic densityMedial temporal regionsAlzheimer's diseaseNeocortical regionsTemporal regionsRelative outcome measuresMedial temporal lobeVivo PET imagingJ bindingOutcome measuresTemporal lobeMagnitude of reductionCN participantsBrain regionsAD participantsDiseasePET imagingConcordant reductionNormal participantsSynaptic vesiclesPerfusionMetabolismSuitable markerParticipantsSimilar patternAssociation of Aβ deposition and regional synaptic density in early Alzheimer’s disease: a PET imaging study with [11C]UCB-J
O’Dell R, Mecca AP, Chen MK, Naganawa M, Toyonaga T, Lu Y, Godek TA, Harris JE, Bartlett HH, Banks ER, Kominek VL, Zhao W, Nabulsi NB, Ropchan J, Ye Y, Vander Wyk BC, Huang Y, Arnsten AFT, Carson RE, van Dyck CH. Association of Aβ deposition and regional synaptic density in early Alzheimer’s disease: a PET imaging study with [11C]UCB-J. Alzheimer's Research & Therapy 2021, 13: 11. PMID: 33402201, PMCID: PMC7786921, DOI: 10.1186/s13195-020-00742-y.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAniline CompoundsBrainCognitive DysfunctionHumansPositron-Emission TomographyConceptsRegional Aβ depositionAβ depositionEarly Alzheimer's diseaseSynaptic lossSynaptic densityAlzheimer's diseaseDistribution volume ratioPositron emission tomographyHippocampal synaptic densityMild AD dementiaDeposition of AβSignificant inverse associationAmnestic mild cognitive impairmentWhole-brain analysisMild cognitive impairmentCerebellar reference regionPET imaging studiesPlaque burdenAD dementiaInverse associationPostmortem studiesClinical severityNeurodegenerative processesClinical diseaseLarge cohort
2020
In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET
Mecca AP, Chen M, O'Dell RS, Naganawa M, Toyonaga T, Godek TA, Harris JE, Bartlett HH, Zhao W, Nabulsi NB, Vander Wyk B, Varma P, Arnsten AFT, Huang Y, Carson RE, van Dyck C. In vivo measurement of widespread synaptic loss in Alzheimer's disease with SV2A PET. Alzheimer's & Dementia 2020, 16: 974-982. PMID: 32400950, PMCID: PMC7383876, DOI: 10.1002/alz.12097.Peer-Reviewed Original ResearchConceptsWidespread synaptic lossEarly Alzheimer's diseaseSynaptic lossAlzheimer's diseaseSynaptic vesicle glycoprotein 2AGray matter volumeMajor structural correlatePositron emission tomography (PET) imagingEmission Tomography ImagingDistribution volume ratioCerebellar reference regionNeocortical brain regionsSynaptic densityAD progressionConsistent pathologyPotential therapyMatter volumePromising biomarkerCognitive impairmentCN participantsBrain regionsDiseaseTomography imagingNormal participantsStructural correlates
2019
In Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease
Toyonaga T, Smith LM, Finnema SJ, Gallezot JD, Naganawa M, Bini J, Mulnix T, Cai Z, Ropchan J, Huang Y, Strittmatter SM, Carson RE. In Vivo Synaptic Density Imaging with 11C-UCB-J Detects Treatment Effects of Saracatinib in a Mouse Model of Alzheimer Disease. Journal Of Nuclear Medicine 2019, 60: 1780-1786. PMID: 31101744, PMCID: PMC6894376, DOI: 10.2967/jnumed.118.223867.Peer-Reviewed Original ResearchConceptsAPP/PS1 micePS1 miceAlzheimer's diseaseWT miceSynaptic densityC-UCBDrug washoutTreatment effectsPresenilin 1 (PS1) double transgenic miceHippocampal synaptic densityAPP/PS1Double transgenic miceEnd of treatmentWild-type miceAmyloid precursor proteinEarly Alzheimer's diseaseSignificant differencesSUVR-1New PET tracersMild cognitive impairmentAD miceSynaptic deficitsOral gavageAD treatmentHealthy subjects
2018
Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging
Chen MK, Mecca AP, Naganawa M, Finnema SJ, Toyonaga T, Lin SF, Najafzadeh S, Ropchan J, Lu Y, McDonald JW, Michalak HR, Nabulsi NB, Arnsten AFT, Huang Y, Carson RE, van Dyck CH. Assessing Synaptic Density in Alzheimer Disease With Synaptic Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging. JAMA Neurology 2018, 75: 1215-1224. PMID: 30014145, PMCID: PMC6233853, DOI: 10.1001/jamaneurol.2018.1836.Peer-Reviewed Original ResearchConceptsPositron emission tomographic imagingSynaptic vesicle glycoprotein 2ASynaptic densityAlzheimer's diseaseEmission tomographic imagingHigh-resolution PET scanningPET scanningCognitive impairmentDisease-modifying therapiesDisease-modifying treatmentsNormal participantsCross-sectional studyPittsburgh compound BMajor structural correlateAmnestic mild cognitive impairmentMagnetic resonance imagingMild cognitive impairmentJ PET imagingRestoration of synapsesSpecific bindingNeurologic evaluationSynaptic lossDisease stagePostmortem studiesOutcome measures