2023
Trial of Solanezumab in Preclinical Alzheimer’s Disease
Sperling R, Donohue M, Raman R, Rafii M, Johnson K, Masters C, van Dyck C, Iwatsubo T, Marshall G, Yaari R, Mancini M, Holdridge K, Case M, Sims J, Aisen P. Trial of Solanezumab in Preclinical Alzheimer’s Disease. New England Journal Of Medicine 2023, 389: 1096-1107. PMID: 37458272, PMCID: PMC10559996, DOI: 10.1056/nejmoa2305032.Peer-Reviewed Original ResearchConceptsAmyloid-related imaging abnormalitiesPreclinical Alzheimer's diseasePositron emission tomographyBrain amyloid levelsPlacebo groupAmyloid levelsAlzheimer's diseaseF-florbetapir positron emission tomographyGlobal Clinical Dementia Rating (CDR) scoreMini-Mental State ExaminationPrimary end pointClinical Dementia Rating scorePhase 3 trialPreclinical Alzheimer's cognitive composite scoresDementia Rating scoreYears of ageForms of amyloidBrain positron emission tomographyImaging abnormalitiesCognitive composite scoreMean ageFamily historyMean changePersons 65State ExaminationRelationships of in vivo brain norepinephrine transporter and age, BMI, and gender
Koohsari S, Sadabad F, Pittman B, Gallezot J, Carson R, van Dyck C, Li C, Potenza M, Matuskey D. Relationships of in vivo brain norepinephrine transporter and age, BMI, and gender. Synapse 2023, 77: e22279. PMID: 37382240, PMCID: PMC10416616, DOI: 10.1002/syn.22279.Peer-Reviewed Original ResearchConceptsBody mass indexMultilinear reference tissue model 2Gender-related differencesBrain norepinephrine transportersNorepinephrine transporterAge-related declineStructural MR scansBrain regionsReference tissue model 2Mass indexRaphe nucleusLocus coeruleusOccipital cortexBMI relationshipHealthy adultsHigh-resolution research tomographAvailable radiotracersHealthy participantsMR scansAgeAnatomic templateReference regionNegative associationNet availabilityPotential agePrincipal 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 patternsLongitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease
Chen C, McCullough A, Gordon B, Joseph-Mathurin N, Flores S, McKay N, Hobbs D, Hornbeck R, Fagan A, Cruchaga C, Goate A, Perrin R, Wang G, Li Y, Shi X, Xiong C, Pontecorvo M, Klein G, Su Y, Klunk W, Jack C, Koeppe R, Snider B, Berman S, Roberson E, Brosch J, Surti G, Jiménez-Velázquez I, Galasko D, Honig L, Brooks W, Clarnette R, Wallon D, Dubois B, Pariente J, Pasquier F, Sanchez-Valle R, Shcherbinin S, Higgins I, Tunali I, Masters C, van Dyck C, Masellis M, Hsiung R, Gauthier S, Salloway S, Clifford D, Mills S, Supnet-Bell C, McDade E, Bateman R, Benzinger T. Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir PET in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer’s disease. European Journal Of Nuclear Medicine And Molecular Imaging 2023, 50: 2669-2682. PMID: 37017737, PMCID: PMC10330155, DOI: 10.1007/s00259-023-06209-0.Peer-Reviewed Original ResearchConceptsStandardized uptake value ratioPhase 2/3 clinical trialsPositron emission tomographyAnti-Aβ monoclonal antibodyClinical trialsPlacebo armDrug effectsLongitudinal changesMonoclonal antibodiesGlobal cortical standardized uptake value ratioHead comparisonCortical standardized uptake value ratioRegional standardized uptake value ratiosAβ positron emission tomographyAmyloid-β positron emission tomographyAlzheimer's disease clinical trialsPET imagingUptake value ratioAβ PET imagingSimulated clinical trialTwo-sample t-testDrug armPittsburgh CompoundPET scansWelch two sample t-test
2022
Aging of the brain in bipolar disorder: Illness- and onset-related effects in cortical thickness and subcortical gray matter volume
Villa L, Colic L, Kim J, Sankar A, Goldman D, Lessing B, Pittman B, Alexopoulos G, van Dyck C, Blumberg H. Aging of the brain in bipolar disorder: Illness- and onset-related effects in cortical thickness and subcortical gray matter volume. Journal Of Affective Disorders 2022, 323: 875-883. PMID: 36526112, PMCID: PMC9839524, DOI: 10.1016/j.jad.2022.12.026.Peer-Reviewed Original ResearchConceptsGray matter volumeOccipital cortical thicknessSubcortical gray matter volumesCortical thicknessBipolar disorderMatter volumeOlder adultsOnset of BDIndividuals age 40Striatal gray matter volumeGray matter reductionsOnset bipolar disorderGray matter decreasesPrefrontal cortical thicknessStructural brain differencesHigh suicide riskCross-sectional designHealthy controlsCognitive dysfunctionTreatment resistanceAge 40Striatal volumeSevere symptomsSuicide attempt historySuicide attemptsSynaptic 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 ResearchPleiotropic effects of telomere length loci with brain morphology and brain tissue expression
Pathak GA, Wendt FR, Levey DF, Mecca AP, van Dyck CH, Gelernter J, Polimanti R. Pleiotropic effects of telomere length loci with brain morphology and brain tissue expression. Human Molecular Genetics 2021, 30: 1360-1370. PMID: 33831179, PMCID: PMC8255129, DOI: 10.1093/hmg/ddab102.Peer-Reviewed Original ResearchConceptsMethylation expressionGenetic variantsMapping gene functionTelomere lengthChromatin associationChromatin profilesGene functionGenetic colocalizationGene mappingGenomic relationshipsNeuropsychiatric traitsPleiotropic rolesDrug-gene interactionsCertain lociBrain tissue expressionGenesLociPleiotropic effectsBrain morphology measuresNucleotide polymorphismsAncestry populationsTissue expressionPhenotypic associationsPleiotropyAncestry groups
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 correlatesPET 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
2017
The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas CD, Carlyle BC, Leslie S, Preuss TM, Crimins JL, Huttner AJ, van Dyck C, Rosene DL, Nairn AC, Arnsten AFT. The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology. Alzheimer's & Dementia 2017, 14: 680-691. PMID: 29241829, PMCID: PMC6178089, DOI: 10.1016/j.jalz.2017.11.005.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseCortical pathologyEntorhinal cortexAnimal modelsBraak stage III/IVAlzheimer's diseaseStage III/IVRhesus macaquesProgression of tauAlzheimer-like pathologyPrimary visual cortexSequence of tauDorsolateral prefrontal cortexTau pathologyPreventive strategiesAssociation cortexVisual cortexPrefrontal cortexCortexPathologyDiseaseOld animalsProtein kinase A (PKA) phosphorylationGenetic insultsMacaques
2009
123I-5-IA-85380 SPECT Imaging of Nicotinic Receptors in Alzheimer Disease and Mild Cognitive Impairment
Mitsis EM, Reech KM, Bois F, Tamagnan GD, MacAvoy MG, Seibyl JP, Staley JK, van Dyck CH. 123I-5-IA-85380 SPECT Imaging of Nicotinic Receptors in Alzheimer Disease and Mild Cognitive Impairment. Journal Of Nuclear Medicine 2009, 50: 1455-1463. PMID: 19690024, DOI: 10.2967/jnumed.109.064030.Peer-Reviewed Original ResearchConceptsAdvanced Alzheimer's diseaseMild cognitive impairmentHealthy control subjectsControl subjectsCognitive impairmentAge-matched healthy control subjectsAlzheimer's diseaseBrain regionsEffect of diagnosisNicotinic acetylcholine receptorsLate-stage phenomenonCholinergic reductionIA-85380Effect of ageUnivariate analysisNicotinic receptorsAnterior cingulateConstant infusionAcetylcholine receptorsTrail Making TestMultivariate analysisNeuropsychologic variablesDiagnostic groupsSignificant overall effectSPECT imagingRegional distribution and behavioral correlates of 5-HT2A receptors in Alzheimer's disease with [18F]deuteroaltanserin and PET
Santhosh L, Estok KM, Vogel RS, Tamagnan GD, Baldwin RM, Mitsis EM, MacAvoy MG, Staley JK, van Dyck CH. Regional distribution and behavioral correlates of 5-HT2A receptors in Alzheimer's disease with [18F]deuteroaltanserin and PET. Psychiatry Research 2009, 173: 212-217. PMID: 19682865, DOI: 10.1016/j.pscychresns.2009.03.007.Peer-Reviewed Original ResearchConceptsPositron emission tomographyAD patient samplesAlzheimer's diseaseAD patientsAnterior cingulateBehavioral symptomsBrain serotonin 2A (5-HT(2A)) receptorsPatient samplesConstant infusion paradigmSerotonin 2A receptorProbable Alzheimer's diseaseMajor behavioral symptomsBehavioral correlatesInfusion paradigmPostmortem studiesPsychotic symptomsElderly controlsMRI scansSubcortical regionsSerotonergic dysregulationEmission tomographyPatientsDiseaseInterest analysisSymptoms
2008
Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT
Mitsis EM, Cosgrove KP, Staley JK, Bois F, Frohlich EB, Tamagnan GD, Estok KM, Seibyl JP, van Dyck CH. Age-related decline in nicotinic receptor availability with [123I]5-IA-85380 SPECT. Neurobiology Of Aging 2008, 30: 1490-1497. PMID: 18242781, PMCID: PMC3523217, DOI: 10.1016/j.neurobiolaging.2007.12.008.Peer-Reviewed Original ResearchConceptsHigh-affinity nicotineEffect of ageReceptor availabilityBrain regionsNicotinic acetylcholine receptor availabilityConstant infusion paradigmHuman postmortem studiesHuman subjectsSingle photon emissionIA-85380NAChR availabilityAge-related declineInfusion paradigmPostmortem studiesPostmortem reportsAgePhoton emissionNicotinePearson correlationCognitive agingSubjectsLinear regressionNonsmokersBolusNAChRs
2001
Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and [18F]deuteroaltanserin
Soares J, van Dyck C, Tan P, Zoghbi S, Garg P, Soufer R, Baldwin R, Fujita M, Staley J, Fu X, Amici L, Seibyl J, Innis R. Reproducibility of in vivo brain measures of 5-HT2A receptors with PET and [18F]deuteroaltanserin. Psychiatry Research 2001, 106: 81-93. PMID: 11306248, DOI: 10.1016/s0925-4927(01)00071-3.Peer-Reviewed Original ResearchConceptsTest/retest reproducibilityPositron emission tomographyCortical brain areasIntra-class correlation coefficientRetest reproducibilityBrain areasBrain measuresHealthy human subjectsMean intra-class correlation coefficientOutcome measuresConstant infusionParent tracerBlood measurementsEmission tomographyNeuropsychiatric disordersPET measuresReceptorsHuman subjectsPET acquisitionMean intraEquilibrium imagingImaging methodInfusionBolusRTComparison of [18F]altanserin and [18F]deuteroaltanserin for PET imaging of serotonin2A receptors in baboon brain: pharmacological studies
Staley J, Van Dyck C, Tan P, Tikriti M, Ramsby Q, Klump H, Ng C, Garg P, Soufer R, Baldwin R, Innis R. Comparison of [18F]altanserin and [18F]deuteroaltanserin for PET imaging of serotonin2A receptors in baboon brain: pharmacological studies. Nuclear Medicine And Biology 2001, 28: 271-279. PMID: 11323237, DOI: 10.1016/s0969-8051(00)00212-2.Peer-Reviewed Original ResearchConceptsReceptor antagonist SR 46349BSerotonin2A receptorsSR 46349BReceptor radiotracerPharmacological specificityTime-activity curvesConstant infusionBaboon brainCortical activityDistribution volumePharmacological studiesPET imagingRadiotracerBrainReceptorsBaboonsPET imagesRegional distributionFenfluramineInfusionBolusNeuroimaging in alzheimer’s disease: Relevance for treatment
van Dyck C. Neuroimaging in alzheimer’s disease: Relevance for treatment. Current Psychiatry Reports 2001, 3: 13-19. PMID: 11177754, DOI: 10.1007/s11920-001-0066-2.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAD patientsRegional cerebral glucose metabolismRegional cerebral blood flowApolipoprotein E e4 alleleAnti-amyloid therapiesCerebral glucose metabolismDisease-modifying agentsCentral cholinergic neurotransmissionWhole brain atrophyCerebral blood flowPutative disease-modifying agentsWidespread clinical testingStructural magnetic resonanceBrain atrophyPrevention therapyInvestigational trialsAsymptomatic subjectsEfficacy measuresCholinergic neurotransmissionE4 alleleSenile plaquesDrug dosingOutcome measuresBlood flow
2000
Equilibrium modeling of 5-ht2a receptors with [18f]deuteroaltanserin and pet: feasibility of a constant infusion paradigm
van Dyck C, Soares J, Tan P, Staley J, Baldwin R, Amici L, Fu X, Garg P, Seibyl J, Charney D, Innis R. Equilibrium modeling of 5-ht2a receptors with [18f]deuteroaltanserin and pet: feasibility of a constant infusion paradigm. Nuclear Medicine And Biology 2000, 27: 715-722. PMID: 11150702, DOI: 10.1016/s0969-8051(00)00160-8.Peer-Reviewed Original ResearchConceptsSpecific brain uptakeConstant infusion paradigmBrain uptakeInfusion paradigmConstant infusionPromising positron emission tomography (PET) ligandPositron emission tomography (PET) ligandVenous blood samplingHealthy male subjectsSerotonin 2A receptorStable radiotracerCerebellar ratioInfusion periodBlood samplingTomography ligandH postinjectionTime-activity curvesParent tracerLinear regression analysisMale subjectsPET radioligandSlow metabolismHuman subjectsBrain activityRegression analysis
1999
[123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia
Verhoeff N, Soares J, D’Souza C, Gil R, Degen K, Abi-Dargham A, Zoghbi S, Fujita M, Rajeevan N, Seibyl J, Krystal J, van Dyck C, Charney D, Innis R. [123I]Iomazenil SPECT benzodiazepine receptor imaging in schizophrenia. Psychiatry Research 1999, 91: 163-173. PMID: 10641580, DOI: 10.1016/s0925-4927(99)00027-x.Peer-Reviewed Original ResearchConceptsDuration of illnessHealthy control subjectsControl subjectsGamma-aminobutyric acidLeft precentral gyrusSuperior occipital gyrusPANSS scoresPrecentral gyrusOccipital gyrusSignificant differencesTotal brain uptakeNon-smoking patientsGray matter atrophyConstant infusion paradigmPathophysiology of schizophreniaCortical brain regionsSingle photon emissionTypical antipsychoticsAtypical antipsychoticsCigarette smokingInhibitory neurotransmissionBrain uptakeInfusion paradigmMatter atrophyPostmortem studies
1998
Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography
Malison R, Price L, Berman R, van Dyck C, Pelton G, Carpenter L, Sanacora G, Owens M, Nemeroff C, Rajeevan N, Baldwin R, Seibyl J, Innis R, Charney D. Reduced brain serotonin transporter availability in major depression as measured by [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane and single photon emission computed tomography. Biological Psychiatry 1998, 44: 1090-1098. PMID: 9836013, DOI: 10.1016/s0006-3223(98)00272-8.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntidepressive AgentsBrainBrain StemCarrier ProteinsCocaineDepressive DisorderFemaleHumansMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNerve Tissue ProteinsParoxetinePsychiatric Status Rating ScalesSerotoninSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-PhotonConceptsDepressed patientsMajor depressionHealthy subjectsBrain serotonin transporter availabilitySerotonin transporterBeta-CIT SPECTDensity of brainPost-mortem brain tissuePathophysiology of depressionSerotonin transporter availabilityUnipolar major depressionBeta-CIT bindingSingle photon emissionSerotonergic neuronsBrain uptakeSERT availabilityTransporter availabilityBeta-CITBrain tissueCarbomethoxy-3βPatientsBlood plateletsDepressionPhoton emissionSignificant reduction