2024
Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease
Honig L, Sabbagh M, van Dyck C, Sperling R, Hersch S, Matta A, Giorgi L, Gee M, Kanekiyo M, Li D, Purcell D, Dhadda S, Irizarry M, Kramer L. Updated safety results from phase 3 lecanemab study in early Alzheimer’s disease. Alzheimer's Research & Therapy 2024, 16: 105. PMID: 38730496, PMCID: PMC11084061, DOI: 10.1186/s13195-024-01441-8.Peer-Reviewed Original ResearchConceptsOpen-label extensionInfusion-related reactionsIntracerebral hemorrhageAdverse eventsAmyloid-related imaging abnormalitiesARIA-HParallel-group studyClinical laboratory parametersMonths of treatmentMild-to-moderateMagnetic resonance imagingHomozygous participantsAPOE e4 carriersDouble-blindPlacebo-controlledLaboratory parametersStudy treatmentARIA-E.Imaging abnormalitiesOptimal patient carePhysical examinationSafety resultsClinical trialsHemosiderin depositionResonance imaging
2023
Relationships 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 age
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
Anti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise
van Dyck CH. Anti-Amyloid-β Monoclonal Antibodies for Alzheimer’s Disease: Pitfalls and Promise. Biological Psychiatry 2017, 83: 311-319. PMID: 28967385, PMCID: PMC5767539, DOI: 10.1016/j.biopsych.2017.08.010.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAmyloid-related imaging abnormalitiesPutative disease-modifying treatmentsMonoclonal antibodiesOngoing prevention trialsDisease-modifying treatmentsPresymptomatic Alzheimer's diseaseImaging abnormalitiesPrevention trialsClinical efficacyPassive immunizationClinical trialsTherapeutic approachesDisease processPreclinical stageAβ-MAbNew trialsDiseaseAdditional studiesTrialsBest treatmentMAbsTreatmentAntibodiesConformation of Aβ
2012
Safety and biomarker effects of solanezumab in patients with Alzheimer's disease
Farlow M, Arnold SE, van Dyck C, Aisen PS, Snider BJ, Porsteinsson AP, Friedrich S, Dean RA, Gonzales C, Sethuraman G, DeMattos RB, Mohs R, Paul SM, Siemers ER. Safety and biomarker effects of solanezumab in patients with Alzheimer's disease. Alzheimer's & Dementia 2012, 8: 261-271. PMID: 22672770, DOI: 10.1016/j.jalz.2011.09.224.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedCognition DisordersDose-Response Relationship, DrugDouble-Blind MethodElectroencephalographyEnzyme-Linked Immunosorbent AssayFemaleFollow-Up StudiesHumansMaleMiddle AgedNeuropsychological TestsPeptide FragmentsPsychiatric Status Rating ScalesPyridinesTomography, Emission-Computed, Single-PhotonTreatment OutcomeConceptsAlzheimer's Disease Assessment Scale-cognitive portionAntibody administrationDose-dependent mannerAlzheimer's diseaseAntibody treatmentAnti-β-amyloid antibodiesPlacebo-controlled clinical trialMagnetic resonance imaging (MRI) scansCerebrospinal fluid examinationClinical laboratory valuesActive treatment periodCSF cell countResonance imaging scansModerate Alzheimer's diseaseDose-dependent increaseMagnetic resonance imagingWeekly infusionsAdverse eventsFluid examinationImaging scansClinical trialsLaboratory valuesTreatment periodAmyloid plaquesCell count
2009
Regional 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 methodInfusionBolusRTNeuroimaging 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
Age-related decline in central serotonin transporter availability with [123I]β-CIT SPECT
van Dyck C, Malison R, Seibyl J, Laruelle M, Klumpp H, Zoghbi S, Baldwin R, Innis R. Age-related decline in central serotonin transporter availability with [123I]β-CIT SPECT. Neurobiology Of Aging 2000, 21: 497-501. PMID: 10924762, DOI: 10.1016/s0197-4580(00)00152-4.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAgingBrain ChemistryBrain StemCarrier ProteinsCocaineDiencephalonFemaleHumansIodine RadioisotopesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNerve Tissue ProteinsReference ValuesSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-PhotonConceptsSERT availabilitySerotonin transporterCentral serotonin transporter availabilityHealthy control subjectsSerotonin transporter availabilitySignificant inverse correlationCentral serotonin transportersAge range 18Single photon emissionBeta-carbomethoxy-3 betaEffect of ageAge-related declineBrain uptakeCIT SPECTControl subjectsPostmortem studiesTransporter availabilityHuman brainstemLinear regression analysisInverse correlationAgeHuman subjectsRegression analysisPhoton emissionPresent studyDopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT
Laruelle M, Abi-Dargham A, van Dyck C, Gil R, D’Souza D, Krystal J, Seibyl J, Baldwin R, Innis R. Dopamine and serotonin transporters in patients with schizophrenia: an imaging study with [123I]β-CIT. Biological Psychiatry 2000, 47: 371-379. PMID: 10704949, DOI: 10.1016/s0006-3223(99)00257-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsBrain StemCarrier ProteinsCase-Control StudiesCocaineDopamineDopamine Plasma Membrane Transport ProteinsFemaleHumansIodine RadioisotopesMaleMembrane GlycoproteinsMembrane Transport ProteinsMiddle AgedNeostriatumNerve Tissue ProteinsSchizophreniaSerotoninSerotonin Plasma Membrane Transport ProteinsTomography, Emission-Computed, Single-PhotonConceptsAmphetamine-induced dopamine releaseStriatal dopamine transporterDopamine transporterControl subjectsDAT densityDopamine releaseNegative symptomsStriatal DAT densityDuration of illnessDopamine nerve terminalsHealthy control subjectsSerotonin transporter densityCohort of subjectsRelative deficitSingle photon emissionNeurodegenerative processesPostmortem studiesNerve terminalsSerotonin functionTrend-level associationReceptor radiotracerPatientsDopamine functionLower striatalTransporter densityEstrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease: A Randomized Controlled Trial
Mulnard R, Cotman C, Kawas C, van Dyck C, Sano M, Doody R, Koss E, Pfeiffer E, Jin S, Gamst A, Grundman M, Thomas R, Thal L, Study F. Estrogen Replacement Therapy for Treatment of Mild to Moderate Alzheimer Disease: A Randomized Controlled Trial. JAMA 2000, 283: 1007-1015. PMID: 10697060, DOI: 10.1001/jama.283.8.1007.Peer-Reviewed Original ResearchConceptsEstrogen replacement therapyModerate Alzheimer's diseaseSecondary outcome measuresReplacement therapyAlzheimer's diseaseOutcome measuresClinical trialsPlacebo-controlled clinical trialMini-Mental State Examination scoreAlzheimer's Disease Cooperative StudyPrevention of ADClinical Dementia Rating ScaleClinical Global ImpressionPrimary outcome measureTreatment of mildSmall clinical trialsRole of estrogenState Examination scoreDementia Rating ScaleCGIC scoresEstrogen groupPlacebo groupControlled TrialsFunctional outcomeGlobal Impression
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
1997
Ciliary neurotrophic factor null allele frequencies in schizophrenia, affective disorders, and Alzheimer's disease
Gelernter J, Van Dyck C, van Kammen D, Malison R, Price L, Cubells J, Berman R, Charney D, Heninger G. Ciliary neurotrophic factor null allele frequencies in schizophrenia, affective disorders, and Alzheimer's disease. American Journal Of Medical Genetics 1997, 74: 497-500. PMID: 9342199, DOI: 10.1002/(sici)1096-8628(19970919)74:5<497::aid-ajmg8>3.0.co;2-l.Peer-Reviewed Original ResearchThe acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer’s disease
van Dyck C, Lin C, Robinson R, Cellar J, Smith E, Nelson J, Arnsten A, Hoffer P. The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer’s disease. Psychopharmacology 1997, 132: 217-226. PMID: 9292621, DOI: 10.1007/s002130050339.Peer-Reviewed Original ResearchConceptsRegional cerebral blood flowParietal regional cerebral blood flowCerebral blood flowAlzheimer's diseaseAD patientsBlood flowDouble-blind trialWeeks of treatmentAD drug therapyProbable Alzheimer's diseaseParietal association cortexSingle photon emissionPlacebo TIDRCBF abnormalitiesCholinergic drugsDrug therapyHealthy controlsRCBF ratiosPharmacological interventionsHealthy subjectsAssociation cortexPatientsLinopirdineBrain regionsNeuropsychological function