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 ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBiomarkersFluorodeoxyglucose F18HumansMicePilot ProjectsPositron-Emission TomographyConceptsMild 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 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
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 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 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 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
Alzheimer's & Dementia: The Journal of the Alzheimer's Association
Mecca AP, van Dyck C. Alzheimer's & Dementia: The Journal of the Alzheimer's Association. Alzheimer's & Dementia 2020, 17: 316-317. PMID: 33047474, PMCID: PMC7962853, DOI: 10.1002/alz.12190.Peer-Reviewed Original ResearchIn 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 correlatesAmyloid: From Starch to Finish
Krystal HL, Ross DA, Mecca AP. Amyloid: From Starch to Finish. Biological Psychiatry 2020, 87: e23-e24. PMID: 32299582, PMCID: PMC7449531, DOI: 10.1016/j.biopsych.2020.02.1182.Peer-Reviewed Original ResearchPET imaging of mGluR5 in Alzheimer’s disease
Mecca AP, McDonald JW, Michalak HR, Godek TA, Harris JE, Pugh EA, Kemp EC, Chen MK, Salardini A, Nabulsi NB, Lim K, Huang Y, Carson RE, Strittmatter SM, van Dyck CH. PET imaging of mGluR5 in Alzheimer’s disease. Alzheimer's Research & Therapy 2020, 12: 15. PMID: 31954399, PMCID: PMC6969979, DOI: 10.1186/s13195-020-0582-0.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseaseAlzheimer's diseaseMild cognitive impairmentBrain amyloidHippocampus of ADPositron emission tomography radioligandSubtype 5 receptorsMild AD dementiaGray matter atrophyAssociation cortical regionsAmnestic mild cognitive impairmentImportant therapeutic targetCerebellum reference regionDynamic PET scansHippocampal mGluR5MethodsSixteen individualsMGluR5 bindingSynaptotoxic actionAD dementiaAD pathogenesisMatter atrophyInitial administrationAD groupSynaptic transmissionEntorhinal cortex
2019
Statin Use and Risk of Cognitive Decline in the ADNI Cohort
Kemp EC, Ebner MK, Ramanan S, Godek TA, Pugh EA, Bartlett HH, McDonald JW, Mecca MC, van Dyck CH, Mecca AP, Initiative T. Statin Use and Risk of Cognitive Decline in the ADNI Cohort. American Journal Of Geriatric Psychiatry 2019, 28: 507-517. PMID: 31806426, PMCID: PMC7170771, DOI: 10.1016/j.jagp.2019.11.003.Peer-Reviewed Original Research1ciii AD molecular: Molecular imaging of Alzheimer's disease: PET imaging of neurotransmitter systems
Mecca AP. 1ciii AD molecular: Molecular imaging of Alzheimer's disease: PET imaging of neurotransmitter systems. Progress In Nucleic Acid Research And Molecular Biology 2019, 165: 139-165. PMID: 31481161, DOI: 10.1016/bs.pmbts.2019.04.003.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseHumansMolecular ImagingNeurotransmitter AgentsPositron-Emission TomographyReceptor, Metabotropic Glutamate 5SynapsesConceptsMagnetic resonance imagingDisease pathogenesisSynaptic protein changesAlzheimer's disease (AD) pathogenesisEmission Tomography ImagingPositron emission tomography (PET) imagingNeurotransmitter lossMolecular imagingNeuropsychiatric symptomsImportant etiologyAssessment of cognitionDisease progressionNeurotransmitter systemsAmyloid βTherapeutic efficacyAlzheimer's diseaseResonance imagingSynaptic proteinsTau aggregatesValuable markerStudy of ADVivo molecular imagingTomography imagingPET imagingDisease
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 measuresEffects of Normative Adjustments to the Montreal Cognitive Assessment
Pugh EA, Kemp EC, van Dyck CH, Mecca AP, Sharp ES, Initiative F. Effects of Normative Adjustments to the Montreal Cognitive Assessment. American Journal Of Geriatric Psychiatry 2018, 26: 1258-1267. PMID: 30314940, PMCID: PMC6779033, DOI: 10.1016/j.jagp.2018.09.009.Peer-Reviewed Original ResearchSleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort
Mecca AP, Michalak HR, McDonald JW, Kemp EC, Pugh EA, Becker ML, Mecca MC, van Dyck CH. Sleep Disturbance and the Risk of Cognitive Decline or Clinical Conversion in the ADNI Cohort. Dementia And Geriatric Cognitive Disorders 2018, 45: 232-242. PMID: 29886490, PMCID: PMC6178799, DOI: 10.1159/000488671.Peer-Reviewed Original ResearchConceptsMild cognitive impairmentCognitive declineSleep disturbancesSubsequent cognitive declineExecutive functionGlobal cognitionCognitionMCI participantsCognitive impairmentNormal cognitionEarly mild cognitive impairmentClinical conversionLongitudinal cohort studyYears of ageDiagnostic conversionADNI cohortCohort studyAlzheimer's diseaseSecondary analysisMemoryParticipantsImpairmentDeclineAdultsIndividuals
2017
Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease
Mecca AP, Barcelos NM, Wang S, Brück A, Nabulsi N, Planeta-Wilson B, Nadelmann J, Benincasa AL, Ropchan J, Huang Y, Gelernter J, Van Ness PH, Carson RE, van Dyck CH. Cortical β-amyloid burden, gray matter, and memory in adults at varying APOE ε4 risk for Alzheimer's disease. Neurobiology Of Aging 2017, 61: 207-214. PMID: 29111487, PMCID: PMC5722236, DOI: 10.1016/j.neurobiolaging.2017.09.027.Peer-Reviewed Original ResearchConceptsΒ-amyloid burdenMiddle-aged individualsAβ burdenEpisodic memory performanceCognitive declineGM fractionCortical β-amyloid burdenBrain magnetic resonance imagingFirst-degree family historyCortical Aβ burdenGray matter fractionNormal middle-aged individualsSubsequent cognitive declineMagnetic resonance imagingPositron emission tomographyAPOE ε3ε3Cortical AβCerebral amyloidosisAPOE genotypeFamily historyPreclinical ADMemory performanceNeuropsychological testingAlzheimer's diseaseGray matter