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 imagingWhole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease
Xicota L, Cosentino S, Vardarajan B, Mayeux R, Perls T, Andersen S, Zmuda J, Thyagarajan B, Yashin A, Wojczynski M, Krinsky‐McHale S, Handen B, Christian B, Head E, Mapstone M, Schupf N, Lee J, Barral S, Study T, Abner E, Adams P, Aguirre A, Albert M, Albin R, Allen M, Alvarez L, Andrews H, Apostolova L, Arnold S, Asthana S, Atwood C, Ayres G, Barber R, Barnes L, Barral S, Bartlett J, Beach T, Becker J, Beecham G, Benchek P, Bennett D, Bertelson J, Biber S, Bird T, Blacker D, Boeve B, Bowen J, Boxer A, Brewer J, Burke J, Burns J, Bush W, Buxbaum J, Byrd G, Cantwell L, Cao C, Carlsson C, Carrasquillo M, Chan K, Chasse S, Chen Y, Chesselet M, Chin N, Chui H, Chung J, Craft S, Crane P, Cranney M, Cruchaga C, Cuccaro M, Culhane J, Cullum C, Darby E, Davis B, De Jager P, DeCarli C, DeToledo J, Dickson D, Dobbins N, Duara R, Ertekin‐Taner N, Evans D, Faber K, Fairchild T, Fallin D, Fallon K, Fardo D, Farlow M, Farrell J, Farrer L, Fernandez‐Hernandez V, Foroud T, Frosch M, Galasko D, Gamboa A, Gauthreaux K, Gefen T, Geschwind D, Ghetti B, Gilbert J, Goate A, Grabowski T, Graff‐Radford N, Griswold A, Haines J, Hakonarson H, Hall K, Hall J, Hamilton R, Hamilton‐Nelson K, Han X, Harari O, Hardy J, Harrell L, Head E, Henderson V, Hernandez M, Honig L, Huebinger R, Huentelman M, Hulette C, Hyman B, Hynan L, Ibanez L, Jarvik G, Jayadev S, Jin L, Johnson K, Johnson L, Jones B, Jun G, Kamboh M, Kang M, Karydas A, Katz M, Kauwe J, Kaye J, Keene C, Keller B, Khaleeq A, Kim R, Knebl J, Kowall N, Kramer J, Kukull W, Kunkle B, Kuzma A, LaFerla F, Lah J, Larson E, Lerch M, Lerner A, Leung Y, Leverenz J, Levey A, Lieberman A, Lipton R, Lopez O, Lunetta K, Lyketsos C, Mains D, Manly J, Mark L, Marquez D, Marson D, Martin E, Masliah E, Massman P, Masurkar A, Mayeux R, McCormick W, McCurry S, McDonough S, McKee A, Mesulam M, Mez J, Miller B, Miller C, Mock C, Moghekar A, Montine T, Monuki E, Mooney S, Morris J, Mukherjee S, Myers A, Naj A, Nguyen T, Noble J, Nudelman K, O'Bryant S, Ormsby K, Ory M, Palmer R, Parisi J, Paulson H, Pavlik V, Paydarfar D, Perez V, Pericak‐Vance M, Petersen R, Polk M, Qu L, Quiceno M, Quinn J, Raj A, Rajabli F, Ramanan V, Reiman E, Reisch J, Reitz C, Ringman J, Roberson E, Rodriguear M, Rogaeva E, Rosen H, Rosenberg R, Royall D, Sano M, Saykin A, Schellenberg G, Schneider J, Schneider L, Seeley W, Sherva R, Shibata D, Small S, Smith A, Smith J, Song Y, Spina S, St George‐Hyslop P, Stern R, Stevens A, Strittmatter S, Sultzer D, Swerdlow R, Teich A, Tilson J, Tosto G, Trojanowski J, Troncoso J, Tsuang D, Valladares O, Van Deerlin V, Van Dyck C, Van Eldik L, Vance J, Vardarajan B, Vassar R, Vinters H, Wang L, Weintraub S, Welsh‐Bohmer K, Wheeler N, Wijsman E, Wilhelmsen K, Williams B, Williamson J, Wilms H, Wingo T, Wisniewski T, Woltjer R, Woon M, Younkin S, Yu L, Zhao Y, Zhou X, Zhu C, Aizenstein H, Ances B, Andrews H, Bell K, Birn R, Brickman A, Bulova P, Cheema A, Chen K, Christian B, Clare I, Cohen A, Constantino J, Doran E, Fagan A, Feingold E, Foroud T, Handen B, Harp J, Hartley S, Head E, Henson R, Hom C, Honig L, Ikonomovic M, Johnson S, Jordan C, Kamboh M, Keator D, Klunk W, Kofler J, Krinsky‐McHale S, Lai F, Lao P, Laymon C, Lee J, Lott I, Lupson V, Mapstone M, Mathis C, Minhas D, Nadkarni N, O'Bryant S, Parisi M, Pang D, Petersen M, Price J, Pulsifer M, Rafii M, Reiman E, Rizvi B, Rosas H, Ryan L, Schmitt F, Schupf N, Silverman W, Tudorascu D, Tumuluru R, Varadarajan B, White D, Yassa M, Zaman S, Zhang F. Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 2670-2679. PMID: 38380866, PMCID: PMC11032545, DOI: 10.1002/alz.13718.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseGenes associated with late-onset Alzheimer's diseaseLate-onset Alzheimer's disease riskSeveral single nucleotide polymorphismsVariants associated with late-onset Alzheimer diseaseBeta-amyloidIdentified several single nucleotide polymorphismsWhole-genome sequence analysisGenome sequence analysisLevels of beta-amyloidAlzheimer's diseaseTight linkage disequilibriumMicrotubule associated proteinSingle nucleotide polymorphismsFamily studiesCandidate lociMTUS2Linkage disequilibriumSequence analysisAssociation analysisNucleotide polymorphismsGenetic associationAlzheimer's dementiaAssociated proteinGenetic componentA 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
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 ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedBrainFemaleHumansMalePositron-Emission TomographyConceptsAmyloid-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 ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAniline CompoundsBrainEthylene GlycolsHumansPositron-Emission TomographyConceptsStandardized 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
Hypothalamic Functional Connectivity and Apathy in People with Alzheimer’s Disease and Cognitively Normal Healthy Controls
Chaudhary S, Zhornitsky S, Chao H, van Dyck C, Li C. Hypothalamic Functional Connectivity and Apathy in People with Alzheimer’s Disease and Cognitively Normal Healthy Controls. Journal Of Alzheimer's Disease 2022, 90: 1615-1628. PMID: 36314209, PMCID: PMC10064487, DOI: 10.3233/jad-220708.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesApathyCognitive DysfunctionHumansMagnetic Resonance ImagingConceptsMiddle temporal gyrusMild cognitive impairmentMotivation circuitsFunctional connectivityPath analysisWhole-brain regressionPCu/PCCState functional connectivityTotal scoreTemporal gyrusNeural markersCingulate cortexMemory dysfunctionRSFCHealthy controlsCognitive statusCognitive impairmentAlzheimer's diseaseApathyPrecuneusMemoryRsFCsDepressionScale total scoreCognitive subscoresLecanemab 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 ResearchMeSH KeywordsActivities of Daily LivingAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedCognitionDouble-Blind MethodHumansNootropic AgentsConceptsEarly 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 ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitive DysfunctionHumansTau ProteinsConceptsPlasma 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 sumTwo Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease
Budd Haeberlein S, Aisen P, Barkhof F, Chalkias S, Chen T, Cohen S, Dent G, Hansson O, Harrison K, von Hehn C, Iwatsubo T, Mallinckrodt C, Mummery C, Muralidharan K, Nestorov I, Nisenbaum L, Rajagovindan R, Skordos L, Tian Y, van Dyck C, Vellas B, Wu S, Zhu Y, Sandrock A. Two Randomized Phase 3 Studies of Aducanumab in Early Alzheimer’s Disease. The Journal Of Prevention Of Alzheimer's Disease 2022, 9: 197-210. PMID: 35542991, DOI: 10.14283/jpad.2022.30.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, Monoclonal, HumanizedBiomarkersHumansConceptsEarly Alzheimer's diseasePhase 3 studyAlzheimer's diseaseDisease dementiaAmyloid betaDisease pathophysiologyRandomized phase 3 studyClinical Dementia Rating SumCommon adverse eventsSecondary clinical endpointsPrimary outcome measureDose-dependent reductionAlzheimer's disease pathophysiologyAlzheimer's disease dementiaHuman monoclonal antibodyMild cognitive impairmentMild Alzheimer's disease dementiaPrimary endpointSecondary endpointsWeek 78Adverse eventsBiomarker substudyClinical outcomesEfficacy analysisBackgroundAlzheimer’s disease
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 ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, MonoclonalHumansImmunotherapyMiddle AgedConceptsAlzheimer'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