2024
A 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
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 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 patterns
2022
Synaptic 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
2021
Generation 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 ResearchAmyloid-Associated Depression—or Not?
van Dyck CH, O'Dell RS, Mecca AP. Amyloid-Associated Depression—or Not? Biological Psychiatry 2021, 89: 737-738. PMID: 33766236, PMCID: PMC8396710, DOI: 10.1016/j.biopsych.2021.02.008.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 ResearchConceptsSynaptic 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 ResearchConceptsRegional 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
2015
Synthetic Metallochaperone ZMC1 Rescues Mutant p53 Conformation by Transporting Zinc into Cells as an Ionophore
Blanden AR, Yu X, Wolfe AJ, Gilleran JA, Augeri DJ, O'Dell RS, Olson EC, Kimball SD, Emge TJ, Movileanu L, Carpizo DR, Loh SN. Synthetic Metallochaperone ZMC1 Rescues Mutant p53 Conformation by Transporting Zinc into Cells as an Ionophore. Molecular Pharmacology 2015, 87: 825-831. PMID: 25710967, PMCID: PMC4407733, DOI: 10.1124/mol.114.097550.Peer-Reviewed Original ResearchConceptsHuman embryonic kidney cell line 293Mutant p53 conformationEssential zinc ionCell line 293Mutant proteinsP53-R175HPlasma membraneExtracellular environmentP53 conformationTumor suppressorLiving cellsHuman cancersBinding sitesX-ray crystal structureCommon mutationsObserved reactivationCellsZinc ionsMetallochaperoneVivo activityMutantsSuppressorOrganismsProteinR175H
2012
Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone
O’Dell R, Ustine CJ, Cameron DA, Lawless SM, Williams RM, Zipfel WR, Olson EC. Layer 6 cortical neurons require Reelin-Dab1 signaling for cellular orientation, Golgi deployment, and directed neurite growth into the marginal zone. Neural Development 2012, 7: 25. PMID: 22770513, PMCID: PMC3466444, DOI: 10.1186/1749-8104-7-25.Peer-Reviewed Original ResearchConceptsEarly cortical developmentMutant cortexCortical neuronsCortical developmentPial surfaceMarginal zoneApical neuritesL6 neuronsRecombinant ReelinNeocortical neuronsNeuronal somataReelin-Dab1Arbor lengthArbor sizeExplant modelVentricular zonePioneer neuronsMutant neuronsReelinNeuronsConclusionsThese findingsMore primary processesNeuronal orientationCortexNeurite growth