2025
Prognostic value of plasma biomarkers for informing clinical trial design in mild-to-moderate Alzheimer’s disease
Qiu Y, Jacobs D, Messer K, Salmon D, Wellington C, Stukas S, Revta C, Brewer J, Léger G, Askew B, Donahue L, Kaplita S, Coric V, Qureshi I, Feldman H. Prognostic value of plasma biomarkers for informing clinical trial design in mild-to-moderate Alzheimer’s disease. Alzheimer's Research & Therapy 2025, 17: 97. PMID: 40317057, PMCID: PMC12046789, DOI: 10.1186/s13195-025-01745-3.Peer-Reviewed Original ResearchConceptsMild to moderate ADADAS-cog11CDR-SBBaseline plasma NfLAlzheimer's diseasePlasma biomarkersMild-to-moderate Alzheimer's diseasePrognostic valueClinical trialsBaseline NfLPlasma NfLPlacebo-controlled trialCortical volumeConcentrations of plasma biomarkersMethodsPost hoc analysisDesign of clinical trialsClinical outcome dataIncreased ventricular volumeTrial participantsVolumetric MRIBaseline concentrationsEarly disease stagesClinical trial designTrial entry criteriaAD trialsUse of lecanemab and donanemab in the Canadian healthcare system: Evidence, challenges, and areas for future research
Smith E, Phillips N, Feldman H, Borrie M, Ganesh A, Henri-Bhargava A, Desmarais P, Frank A, Badhwar A, Barlow L, Bartha R, Best S, Bethell J, Bhangu J, Black S, Bocti C, Bronskill S, Burhan A, Calon F, Camicioli R, Campbell B, Collins D, Dadar M, DeMarco M, Ducharme S, Duchesne S, Einstein G, Fisk J, Gawryluk J, Grossman L, Ismail Z, Itzhak I, Joshi M, Harrison A, Kröger E, Kumar S, Laforce R, Lanctot K, Lau M, Lee L, Masellis M, Massoud F, Mitchell S, Montero-Odasso M, Barnett K, Nygaard H, Pasternak S, Peters J, Rajah M, Robillard J, Rockwood K, Rosa-Neto P, Seitz D, Soucy J, Trenaman S, Wellington C, Zadem A, Chertkow H, Investigators C. Use of lecanemab and donanemab in the Canadian healthcare system: Evidence, challenges, and areas for future research. The Journal Of Prevention Of Alzheimer's Disease 2025, 12: 100068. PMID: 39893139, PMCID: PMC12184013, DOI: 10.1016/j.tjpad.2025.100068.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCanadaDelivery of Health CareHumansConceptsCanadian healthcare systemStatistically significant group differencesAlzheimer's diseaseMild cognitive impairmentMild dementiaHealthcare systemStage of mild cognitive impairmentQuality evidenceSignificant group differencesMonoclonal antibody therapyTrial publicationsCerebrospinal fluid analysisCognitive impairmentCanadian ConsortiumGroup differencesPositron emission tomographyAntibody therapyImaging abnormalitiesTreatment populationClinical trialsIndividual patientsReview evidenceClinical relevanceTherapyAmyloid-related imaging abnormalities
2024
Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease
Grill J, Tam S, Thai G, Vides B, Pierce A, Green K, Gillen D, Teng E, Kremen S, Beigi M, Rissman R, Léger G, Balasubramanian A, Revta C, Morrison R, Jennings R, Pa J, Zhang J, Jin S, Messer K, Feldman H. Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease. Neurology 2024, 104: e210152. PMID: 39671543, PMCID: PMC11655133, DOI: 10.1212/wnl.0000000000210152.Peer-Reviewed Original ResearchConceptsTau phosphorylationP-tau<sub>181</sub>Histone deacetylasesCDR-SBAlzheimer's diseaseCSF p-tauPrimary outcomeP-tauDiagnosis of mild cognitive impairmentAlzheimer's Disease Assessment ScaleAlzheimer's Disease Cooperative Study-ActivitiesClass III histone deacetylasePrespecified secondary outcomesCellular oxidation-reduction reactionsDisease Assessment ScaleLevels of tauAD biomarkersHolm-Bonferroni procedureMild cognitive impairmentControl type I errorThreonine 231Histone deacetylase inhibitionAcademic clinical centersAssessment ScaleAdverse eventsVaroglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer’s Disease
Feldman H, Messer K, Qiu Y, Sabbagh M, Galasko D, Turner R, Lopez O, Smith A, Durant J, Lupo J, Revta C, Balasubramanian A, Kuehn-Wache K, Wassmann T, Schell-Mader S, Jacobs D, Salmon D, Léger G, DeMarco M, Weber F, Group F. Varoglutamstat: Inhibiting Glutaminyl Cyclase as a Novel Target of Therapy in Early Alzheimer’s Disease. Journal Of Alzheimer’s Disease 2024, 101: s79-s93. PMID: 39422941, PMCID: PMC11494639, DOI: 10.3233/jad-231126.Peer-Reviewed Original ResearchConceptsGlutaminyl cyclasePost-translationallyAlzheimer's diseasePhase 2bEarly phase clinical trialsAmyloid-bCytokine monocyte chemoattractant protein-1Monocyte chemoattractant protein-1Highest tolerated doseLonger-term safetyPhase clinical trialsWeeks of treatmentFirst-in-classTarget of therapyUnique dual mechanismChemoattractant protein-1Interim futility analysisClinical efficacyDisease cascadeProtein 1Electroencephalogram changesOptimal doseClinical trialsAnalysis of cognitive functionHigh dosesA multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease
Galasko D, Farlow M, Lucey B, Honig L, Elbert D, Bateman R, Momper J, Thomas R, Rissman R, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M, Feldman H. A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer’s Disease. Alzheimer's Research & Therapy 2024, 16: 151. PMID: 38970127, PMCID: PMC11225352, DOI: 10.1186/s13195-024-01490-z.Peer-Reviewed Original ResearchConceptsOrally administered small moleculeFractional synthesis rateAscending dose studyDose-dependent loweringIRB-approved protocolEarly ADMini-Mental State ExamDose-dependent effectAlzheimer's diseaseBlood patchDouble-blindWell-toleratedCatheter placementPreclinical modelsLumbar punctureDose studyIntravenous infusionMild cognitive impairmentEvaluate safetyPlacebo participantsCognitive measuresStable isotope labeling kineticsActive drugClinical trialsADAS-Cog12
2023
Efficacy assessment of an active tau immunotherapy in Alzheimer’s disease patients with amyloid and tau pathology: a post hoc analysis of the “ADAMANT” randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial
Cullen N, Novak P, Tosun D, Kovacech B, Hanes J, Kontsekova E, Fresser M, Ropele S, Feldman H, Schmidt R, Winblad B, Zilka N. Efficacy assessment of an active tau immunotherapy in Alzheimer’s disease patients with amyloid and tau pathology: a post hoc analysis of the “ADAMANT” randomised, placebo-controlled, double-blind, multi-centre, phase 2 clinical trial. EBioMedicine 2023, 99: 104923. PMID: 38101301, PMCID: PMC10733085, DOI: 10.1016/j.ebiom.2023.104923.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersHumansImmunotherapyImmunotherapy, Activetau ProteinsConceptsTau pathologyPathological tau proteinsAlzheimer's diseaseDouble-blindPlacebo-controlledCDR-SBTau immunotherapyTau proteinPhase 2 clinical trialAnti-tauPost hoc subgroup analysisAD-related declineDisease patientsSlowing of declineAlzheimer's disease patientsAntibody-dependent mannerAADvac1Post hoc analysisActive immunotherapyTauFull analysisParallel-groupSubgroup analysisBaseline MRIEfficacy assessment
2012
Predicting missing biomarker data in a longitudinal study of Alzheimer disease
Lo R, Jagust W, Aisen P, Jack C, Toga A, Beckett L, Gamst A, Soares H, C. Green R, Montine T, Thomas R, Donohue M, Walter S, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Bandy D, Chen K, Morris J, Lee V, Korecka M, Crawford K, Neu S, Harvey D, Kornak J, Saykin A, Foroud T, Potkin S, Shen L, Buckholtz N, Kaye J, Dolen S, Quinn J, Schneider L, Pawluczyk S, Spann B, Brewer J, Vanderswag H, Heidebrink J, Lord J, Petersen R, Johnson K, Doody R, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig L, Bell K, Morris J, Mintun M, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Tang C, Marzloff G, Toledo-Morrell L, Shah R, Duara R, Varon D, Roberts P, Albert M, Pedroso J, Toroney J, Rusinek H, de Leon M, De Santi S, Doraiswamy P, Petrella J, Aiello M, Clark C, Pham C, Nunez J, Smith C, Given C, Hardy P, Lopez O, Oakley M, Simpson D, Ismail M, Brand C, Richard J, Mulnard R, Thai G, Mc-Adams-Ortiz C, Diaz-Arrastia R, Martin-Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Laubinger M, Bartzokis G, Silverman D, Lu P, Graff-Radford MBBCH N, Parfitt F, Johnson H, Farlow M, Herring S, Hake A, van Dyck C, MacAvoy M, Benincasa A, Chertkow H, Bergman H, Hosein C, Black S, Graham S, Caldwell C, Hsiung G, Feldman H, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Wu C, Johnson N, Mesulam M, Sadowsky C, Martinez W, Villena T, Turner S, Johnson K, Behan K, Sperling R, Rentz D, Johnson K, Rosen A, Tinklenberg J, Ashford W, Sabbagh M, Connor D, Jacobson S, Killiany R, Norbash A, Nair A, Obisesan T, Jayam-Trouth A, Wang P, Lerner A, Hudson L, Ogrocki P, DeCarli C, Fletcher E, Carmichael O, Kittur S, Mirje S, Borrie M, Lee T, Bartha D, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Hendin B, Scharre D, Kataki M, Zimmerman E, Celmins D, Brown A, Gandy S, Marenberg M, Rovner B, Pearlson G, Anderson K, Saykin A, Santulli R, Englert J, Williamson J, Sink K, Watkins F, Ott B, Wu C, Cohen R, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J. Predicting missing biomarker data in a longitudinal study of Alzheimer disease. Neurology 2012, 78: 1376-1382. PMID: 22491869, PMCID: PMC3345787, DOI: 10.1212/wnl.0b013e318253d5b3.Peer-Reviewed Original ResearchAlzheimer DiseaseAmyloid beta-PeptidesBiomarkersCognitive DysfunctionCohort StudiesDementia, VascularFluorodeoxyglucose F18HomocysteineHumansLogistic ModelsLongitudinal StudiesMagnetic Resonance ImagingNeuropsychological TestsPatient DropoutsPeptide FragmentsPositron-Emission TomographyResearch DesignRisk Factorstau Proteins
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