2024
Synaptic loss and its association with symptom severity in Parkinson’s disease
Holmes S, Honhar P, Tinaz S, Naganawa M, Hilmer A, Gallezot J, Dias M, Yang Y, Toyonaga T, Esterlis I, Mecca A, Van Dyck C, Henry S, Ropchan J, Nabulsi N, Louis E, Comley R, Finnema S, Carson R, Matuskey D. Synaptic loss and its association with symptom severity in Parkinson’s disease. Npj Parkinson's Disease 2024, 10: 42. PMID: 38402233, PMCID: PMC10894197, DOI: 10.1038/s41531-024-00655-9.Peer-Reviewed Original ResearchSynaptic density lossPositron emission tomographyBinds to synaptic vesicle glycoprotein 2AAssociated with symptom severityParkinson's diseaseHigh-resolution positron emission tomographySynaptic vesicle glycoprotein 2ADuration of illnessPositron emission tomography scanBrain perfusionIllness durationSymptom severitySeverity of symptomsHC groupSubstantia nigraSynaptic densityLiving brainPD individualsClinical insightsDensity lossPD patientsEmission tomographyBrainSynaptic lossSynapse loss
2023
Decreased 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 kinetics
2022
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1qFeasibility of imaging synaptic density in the human spinal cord using [11C]UCB-J PET
Rossano S, Toyonaga T, Bini J, Nabulsi N, Ropchan J, Cai Z, Huang Y, Carson RE. Feasibility of imaging synaptic density in the human spinal cord using [11C]UCB-J PET. EJNMMI Physics 2022, 9: 32. PMID: 35503134, PMCID: PMC9065222, DOI: 10.1186/s40658-022-00464-0.Peer-Reviewed Original ResearchFull spinal cordSpinal cord injuryHuman spinal cordSpinal cordAmyotrophic lateral sclerosisDistribution volume ratioCervical SCSynaptic densitySynaptic vesicle protein 2ACervical spinal cordBrain gray matterUse of PETBaseline VTWhole-body imagesSynapse lossCord injuryLateral sclerosisInjury severityGray matterNeurodegenerative disordersCordProtein 2AHuman dataDVR valuesCurrent standardSynaptic 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 ResearchConceptsSynaptic 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