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 lossExamining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease
Wang G, Li Y, Xiong C, Benzinger T, Gordon B, Hassenstab J, Aschenbrenner A, McDade E, Clifford D, Libre‐Guerra J, Shi X, Mummery C, van Dyck C, Lah J, Honig L, Day G, Ringman J, Brooks W, Fox N, Suzuki K, Levin J, Jucker M, Delmar P, Bittner T, Bateman R, Team F. Examining amyloid reduction as a surrogate endpoint through latent class analysis using clinical trial data for dominantly inherited Alzheimer's disease. Alzheimer's & Dementia 2024 PMID: 38400532, DOI: 10.1002/alz.13735.Peer-Reviewed Original ResearchLatent classesPositron emission tomographyAmyloid reductionCognitive efficacyLatent class analysisAmyloid positron emission tomographyCognitive outcomesCognitive declineDominantly Inherited Alzheimer's Network Trials UnitSurrogate biomarkerBaseline characteristicsInherited Alzheimer's diseaseMultiple measuresClass analysisEmission tomographyTrials UnitAlzheimer's diseaseClinical trialsSurrogate endpointsTreatment effectsA 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
Feasibility Study for Longitudinal Retinal Imaging in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Trial
Rissman R, Ngolab J, Donohue M, Belsha A, Salazar J, Cohen P, Jaiswal S, Tan V, Aggarwal N, Alber J, Johnson K, Jicha G, van Dyck C, Lah J, Salloway S, Rafii M, Aisen P, Sperling R. Feasibility Study for Longitudinal Retinal Imaging in the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Trial. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079580.Peer-Reviewed Original ResearchAnti-Amyloid TreatmentAsymptomatic Alzheimer's diseaseFeasibility of retinal imagingLongitudinal Evaluation of Amyloid RiskCohort of individualsAlzheimer's diseaseResults ParticipantsAnti-amyloidA4 trialAD-diagnosed patientsRetinal spotsPositron emission tomographyStandardized uptake value ratioAmyloid positron emission tomographyLongitudinal evaluationRisk detectionClinically normal individualsParticipantsPET standardized uptake value ratioFeasibility studyClinicCross-sectionRetinal amyloid depositsAmyloid depositsIndividualsTrial 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 ExaminationLongitudinal 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-testLecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease
Cohen S, van Dyck C, Gee M, Doherty T, Kanekiyo M, Dhadda S, Li D, Hersch S, Irizarry M, Kramer L. Lecanemab Clarity AD: Quality-of-Life Results from a Randomized, Double-Blind Phase 3 Trial in Early Alzheimer’s Disease. The Journal Of Prevention Of Alzheimer's Disease 2023, 10: 771-777. PMID: 37874099, DOI: 10.14283/jpad.2023.123.Peer-Reviewed Original ResearchConceptsZarit Burden InterviewPhase 3 trialEarly Alzheimer's diseaseAlzheimer's diseaseQoL-ADPartner burdenMean changeDouble-blind phase 3 trialCerebrospinal fluid evidenceHumanized IgG1 monoclonal antibodyMarkers of amyloidLife-5 DimensionsHealth-related qualityPhase 3 developmentCare partner burdenLess increaseCerebral amyloid accumulationLess declineYears of ageQuality of lifePositron emission tomographyMild cognitive impairmentIgG1 monoclonal antibodyValuable patientsBurden Interview
2022
Lecanemab in Early Alzheimer’s Disease
van Dyck C, Swanson C, Aisen P, Bateman R, Chen C, Gee M, Kanekiyo M, Li D, Reyderman L, Cohen S, Froelich L, Katayama S, Sabbagh M, Vellas B, Watson D, Dhadda S, Irizarry M, Kramer L, Iwatsubo T. Lecanemab in Early Alzheimer’s Disease. New England Journal Of Medicine 2022, 388: 9-21. PMID: 36449413, DOI: 10.1056/nejmoa2212948.Peer-Reviewed Original ResearchConceptsEarly Alzheimer's diseasePositron emission tomographyDisease Assessment ScaleAlzheimer's diseaseAmyloid burdenAlzheimer's Disease Cooperative Study-ActivitiesAmyloid-related imaging abnormalitiesKey secondary end pointEnd pointAlzheimer's Disease Assessment ScaleClinical Dementia Rating SumHumanized IgG1 monoclonal antibodyMarkers of amyloidInfusion-related reactionsPrimary end pointSecondary end pointsCerebrospinal fluid testingPhase 3 trialBrain amyloid burdenDaily Living ScaleEvidence of amyloidCDR-SB scoresYears of ageMild cognitive impairmentIgG1 monoclonal antibodyPerformance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease
Wilson E, Young C, Ramos Benitez J, Swarovski M, Feinstein I, Vandijck M, Le Guen Y, Kasireddy N, Shahid M, Corso N, Wang Q, Kennedy G, Trelle A, Lind B, Channappa D, Belnap M, Ramirez V, Skylar-Scott I, Younes K, Yutsis M, Le Bastard N, Quinn J, van Dyck C, Nairn A, Fredericks C, Tian L, Kerchner G, Montine T, Sha S, Davidzon G, Henderson V, Longo F, Greicius M, Wagner A, Wyss-Coray T, Poston K, Mormino E, Andreasson K. Performance of a fully-automated Lumipulse plasma phospho-tau181 assay for Alzheimer’s disease. Alzheimer's Research & Therapy 2022, 14: 172. PMID: 36371232, PMCID: PMC9652927, DOI: 10.1186/s13195-022-01116-2.Peer-Reviewed Original ResearchConceptsPlasma p-tau181Alzheimer's Disease Research CenterP-tau181Disease Research CenterAlzheimer's diseasePositron emission tomographyAD dementiaBlood-based biomarker assaysAmyloid positron emission tomographyTreatment monitoringNovel blood-based biomarkersCSF p-tau181P-tau181 concentrationsDisease-modifying therapiesAβ42/Aβ40 ratioBlood-based biomarkersClinical AD diagnosisDetection of ADMild cognitive impairmentStudy cohortCSF biomarkersPlasma levelsAD groupPrognostic performanceCDR sum
2017
Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study
Brumberg J, Küsters S, Al‐Momani E, Marotta G, Cosgrove KP, van Dyck C, Herrmann K, Homola GA, Pezzoli G, Buck AK, Volkmann J, Samnick S, Isaias IU. Cholinergic activity and levodopa‐induced dyskinesia: a multitracer molecular imaging study. Annals Of Clinical And Translational Neurology 2017, 4: 632-639. PMID: 28904985, PMCID: PMC5590520, DOI: 10.1002/acn3.438.Peer-Reviewed Original ResearchLevodopa-induced dyskinesiaNicotinic acetylcholine receptorsSingle photon emissionNondyskinetic patientsDisease patientsCholinergic activityHealthy controlsAcetylcholine receptorsRegional cerebral metabolic activityDeoxyglucose positron emission tomographyExpression of dyskinesiaCerebral metabolic activityStriatal cholinergic activityParkinson's disease patientsBasal ganglia structuresStriatal binding potentialPositron emission tomographyDopaminergic responsivenessAffected sideClinical variablesDyskinetic subjectsCholinergic signalingGanglia structuresMolecular imaging studiesNeuronal excitability
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
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 methodInfusionBolusRT