2024
Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases
Aguero C, Dhaynaut M, Amaral A, Moon S, Neelamegam R, Scapellato M, Carazo-Casas C, Kumar S, El Fakhri G, Johnson K, Frosch M, Normandin M, Gómez-Isla T. Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases. Acta Neuropathologica 2024, 147: 25. PMID: 38280071, PMCID: PMC10822013, DOI: 10.1007/s00401-023-02672-z.Peer-Reviewed Original ResearchConceptsNon-AD tauopathiesTau aggregationTau PET tracersDNA-binding proteinsBinds to neurofibrillary tanglesSecond-generation tau tracersTransactive response DNA-binding proteinSpectrum of neurodegenerative diseasesNeurofibrillary tanglesTau lesionsMelanin-containing cellsTDP-43Binding signalTauopathiesBinding targetsCerebral amyloid angiopathyOff-target bindingB-amyloidBinding patternsNeurodegenerative diseasesTau tracersTauBinding to areasBinding profilesBinding
2023
Association of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults
Hanseeuw B, Jacobs H, Schultz A, Buckley R, Farrell M, Guehl N, Becker J, Properzi M, Sanchez J, Quiroz Y, Vannini P, Sepulcre J, Yang H, Chhatwal J, Gatchel J, Marshall G, Amariglio R, Papp K, Rentz D, Normandin M, Price J, Healy B, El Fakhri G, Sperling R, Johnson K. Association of Pathologic and Volumetric Biomarker Changes With Cognitive Decline in Clinically Normal Adults. Neurology 2023, 101: e2533-e2544. PMID: 37968130, PMCID: PMC10791053, DOI: 10.1212/wnl.0000000000207962.Peer-Reviewed Original ResearchConceptsAssociated with cognitive declineOlder adultsNon-AD pathologyCognitive declineHippocampal volumeCognitive dataPreclinical Alzheimer Cognitive CompositeInferior temporal tauProspective cohort studyClinically normal older adultsHarvard Aging Brain StudyPittsburgh compound B PET scansOvert cognitive impairmentAnalyzed dataNormal older adultsAging Brain StudyClinically normal adultsLongitudinal associationsAlzheimer's diseaseCohort studyMemory impairmentCognitive compositeCognitive impairmentHippocampal atrophyCognitionAssociation of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease
Prokopiou P, Engels-Domínguez N, Schultz A, Sepulcre J, Koops E, Papp K, Marshall G, Normandin M, El Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Association of Novelty-Related Locus Coeruleus Function With Entorhinal Tau Deposition and Memory Decline in Preclinical Alzheimer Disease. Neurology 2023, 101: e1206-e1217. PMID: 37491329, PMCID: PMC10516269, DOI: 10.1212/wnl.0000000000207646.Peer-Reviewed Original ResearchConceptsLC activityMemory declineLocus coeruleusCognitive declineEC tauHarvard Aging Brain StudyHuman neuroimaging studiesSteeper memory declineNoradrenergic brainstem nucleiLongitudinal cognitive dataFunctional MRI dataTau depositionAging Brain StudyPreclinical Alzheimer's diseaseTau progressionCortical tau depositionElevated beta-amyloidInterventions promoting resilienceMild cognitive impairmentExecutive dysfunctionExecutive functionNeuroimaging studiesTau spreadingTemporal cortexCognitive compositeTau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players
Dhaynaut M, Grashow R, Normandin M, Wu O, Marengi D, Terry D, Sanchez J, Weisskopf M, Speizer F, Taylor H, Guehl N, Seshadri S, Beiser A, Daneshvar D, Johnson K, Iverson G, Zafonte R, Fakhri G, Baggish A. Tau Positron Emission Tomography and Neurocognitive Function Among Former Professional American-Style Football Players. Journal Of Neurotrauma 2023, 40: 1614-1624. PMID: 37282582, PMCID: PMC10458363, DOI: 10.1089/neu.2022.0454.Peer-Reviewed Original ResearchConceptsPositron emission tomographyDistribution volume ratioNeuropsychological testsNeurocognitive functionStandardized uptake value ratioControl participantsMeasures of neurocognitive functionStructural magnetic resonance imagingMeasures of memoryDepressive symptom severityMale control participantsEmission tomographyCerebellar gray matterNeuropsychological measuresTau positron emission tomographyExecutive functionSymptom severityBrain regionsEntorhinal cortexRepetitive head impactsP-tauReference regionFormer playersRepetitive head impact exposureMale controls
2022
Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1
Dhaynaut M, Sprugnoli G, Cappon D, Macone J, Sanchez J, Normandin M, Guehl N, Koch G, Paciorek R, Connor A, Press D, Johnson K, Pascual-Leone A, Fakhri G, Santarnecchi E. Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series1. Journal Of Alzheimer's Disease 2022, 85: 1667-1676. PMID: 34958021, PMCID: PMC9023125, DOI: 10.3233/jad-215072.Peer-Reviewed Original ResearchConceptsMicroglia activationGamma spectral powerDecrease of microglia activationNo adverse eventsTranscranial alternating current stimulationSlow disease progressionPlacebo-controlled conditionsPreclinical dataCase seriesAdverse eventsGamma oscillationsElectrophysiological assessmentP-tauMouse modelDisease progressionMesial regionMild to moderate ADAnimal modelsPatientsPET imagingAlzheimer's diseaseSpectral powerAD mouse modelAD patientsProtein clearance
2021
The cortical origin and initial spread of medial temporal tauopathy in Alzheimer’s disease assessed with positron emission tomography
Sanchez J, Becker J, Jacobs H, Hanseeuw B, Jiang S, Schultz A, Properzi M, Katz S, Beiser A, Satizabal C, O'Donnell A, DeCarli C, Killiany R, El Fakhri G, Normandin M, Gómez-Isla T, Quiroz Y, Rentz D, Sperling R, Seshadri S, Augustinack J, Price J, Johnson K. The cortical origin and initial spread of medial temporal tauopathy in Alzheimer’s disease assessed with positron emission tomography. Science Translational Medicine 2021, 13 PMID: 33472953, PMCID: PMC7978042, DOI: 10.1126/scitranslmed.abc0655.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlzheimer DiseaseAmyloid beta-PeptidesHumansPositron-Emission TomographyTau ProteinsTauopathiesConceptsPositron emission tomographyTemporal lobeMedial temporal lobe tauAlzheimer's diseaseMedial temporal lobeStudy of normal agingAssociated with baseline measuresMolecular positron emission tomographyTau-PET signalDegree of clinical impairmentEmission tomographyModel of Alzheimer's diseaseTemporal lobe anatomyCognitive declineClinical impairmentNormal agingAdult participantsStudy of AgingRhinal sulcusBrain pathologyExtratemporal regionsPET measurementsLongitudinal studyTau progressionClinically normal people
2020
Reply to: Fitting of late dynamic [18F]MK6240 PET scans for in vivo tau quantification
Guehl N, Wooten D, El Fakhri G, Normandin M. Reply to: Fitting of late dynamic [18F]MK6240 PET scans for in vivo tau quantification. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 47: 2947-2949. PMID: 32556399, PMCID: PMC8015946, DOI: 10.1007/s00259-020-04927-3.Peer-Reviewed Original Research
2019
Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects
Guehl N, Wooten D, Yokell D, Moon S, Dhaynaut M, Katz S, Moody K, Gharagouzloo C, Kas A, Johnson K, El Fakhri G, Normandin M. Evaluation of pharmacokinetic modeling strategies for in-vivo quantification of tau with the radiotracer [18F]MK6240 in human subjects. European Journal Of Nuclear Medicine And Molecular Imaging 2019, 46: 2099-2111. PMID: 31332496, PMCID: PMC6709592, DOI: 10.1007/s00259-019-04419-z.Peer-Reviewed Original ResearchConceptsReference tissue methodDistribution volume ratioTissue methodIn vivo quantificationPharmacokinetic modeling strategiesArterial plasma input functionMultilinear reference tissue methodsTwo-tissue compartment modelBlood:plasma ratioTissue-to-plasmaPlasma input functionPlasma concentration time courseBlood-based methodMethodsThirty-five subjectsSUV ratioBlood-based analysesData setsArterial input functionPET scansControl subjectsMild cognitive impairmentPlasma ratioRadiometabolite analysisHealthy controlsConcentration time course
2017
[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging
Marquié M, Siao Tick Chong M, Antón-Fernández A, Verwer E, Sáez-Calveras N, Meltzer A, Ramanan P, Amaral A, Gonzalez J, Normandin M, Frosch M, Gómez-Isla T. [F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging. Acta Neuropathologica 2017, 134: 619-628. PMID: 28612291, PMCID: PMC5772971, DOI: 10.1007/s00401-017-1740-8.Peer-Reviewed Original ResearchConceptsNeurofibrillary tanglesNeurofibrillary tau pathologyTau burdenBraak stageStaging of neurofibrillary tanglesBrain regionsAccurate diagnosis of Alzheimer's diseaseTau pathologyPhospho-tauStereotyped spatiotemporal patternBraak NFT stageNeurofibrillary tangle Braak stagePhosphor-screen autoradiographyAlzheimer's diseaseMild cognitive impairmentTau measuresNFT stageCognitively normal controlsObserved patternBraakCognitive impairmentWestern blottingBindingDiagnosis of Alzheimer's diseaseBraak staging of neurofibrillary tanglesPathological correlations of [F‐18]‐AV‐1451 imaging in non‐alzheimer tauopathies
Marquié M, Normandin M, Meltzer A, Chong M, Andrea N, Antón‐Fernández A, Klunk W, Mathis C, Ikonomovic M, Debnath M, Bien E, Vanderburg C, Costantino I, Makaretz S, DeVos S, Oakley D, Gomperts S, Growdon J, Domoto‐Reilly K, Lucente D, Dickerson B, Frosch M, Hyman B, Johnson K, Gómez‐Isla T. Pathological correlations of [F‐18]‐AV‐1451 imaging in non‐alzheimer tauopathies. Annals Of Neurology 2017, 81: 117-128. PMID: 27997036, PMCID: PMC5319193, DOI: 10.1002/ana.24844.Peer-Reviewed Original ResearchConceptsNon-Alzheimer tauopathiesTau lesionsDetection of tau aggregatesBinding to tau lesionsTau measuresPositron emission tomographyMutation carriersTau filamentsProgressive supranuclear palsyTau aggregationPostmortem brain samplesAlzheimer brainsTauopathiesAV-1451Atypical tauopathyBrain regionsOff-target bindingBinding patternsBinding assaysBasal gangliaEntorhinal cortexSubstantia nigraTauMAPT
2016
Pharmacokinetic Evaluation of the Tau PET Radiotracer 18F-T807 (18F-AV-1451) in Human Subjects
Wooten D, Guehl N, Verwer E, Shoup T, Yokell D, Zubcevik N, Vasdev N, Zafonte R, Johnson K, Fakhri G, Normandin M. Pharmacokinetic Evaluation of the Tau PET Radiotracer 18F-T807 (18F-AV-1451) in Human Subjects. Journal Of Nuclear Medicine 2016, 58: 484-491. PMID: 27660144, PMCID: PMC5334185, DOI: 10.2967/jnumed.115.170910.Peer-Reviewed Original ResearchConceptsDistribution volume ratioTraumatic brain injuryMetabolite-corrected arterial input functionPET imagingPlasma radioactivity concentrationsTemporal cortexDynamic PET imagesTotal volume of distributionVolume of distributionTraumatic brain injury subjectsMesial temporal cortexArterial blood samplesPosterior cingulate gyrusFocal uptakeSUV ratioHuman subjectsArterial input functionPosterior corpus callosumBolus injectionPharmacokinetic evaluationDiscovery of a Highly Selective Glycogen Synthase Kinase‐3 Inhibitor (PF‐04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging
Liang S, Chen J, Normandin M, Chang J, Chang G, Taylor C, Trapa P, Plummer M, Para K, Conn E, Lopresti‐Morrow L, Lanyon L, Cook J, Richter K, Nolan C, Schachter J, Janat F, Che Y, Shanmugasundaram V, Lefker B, Enerson B, Livni E, Wang L, Guehl N, Patnaik D, Wagner F, Perlis R, Holson E, Haggarty S, Fakhri G, Kurumbail R, Vasdev N. Discovery of a Highly Selective Glycogen Synthase Kinase‐3 Inhibitor (PF‐04802367) That Modulates Tau Phosphorylation in the Brain: Translation for PET Neuroimaging. Angewandte Chemie International Edition 2016, 55: 9601-9605. PMID: 27355874, PMCID: PMC4983481, DOI: 10.1002/anie.201603797.Peer-Reviewed Original ResearchConceptsGlycogen synthase kinase-3Tau phosphorylationPET neuroimagingPET imaging studiesModulation of tau phosphorylationNon-human primatesRegulate multiple cellular processesModulates tau phosphorylationMultiple cellular processesBrainBrain permeabilityImaging studiesCellular processesDisplaceable bindingKinase-3
2015
Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue
Marquié M, Normandin M, Vanderburg C, Costantino I, Bien E, Rycyna L, Klunk W, Mathis C, Ikonomovic M, Debnath M, Vasdev N, Dickerson B, Gomperts S, Growdon J, Johnson K, Frosch M, Hyman B, Gómez-Isla T. Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue. Annals Of Neurology 2015, 78: 787-800. PMID: 26344059, PMCID: PMC4900162, DOI: 10.1002/ana.24517.Peer-Reviewed Original ResearchConceptsTau filamentsAlzheimer brainsTDP-43Paired helical filamentsDNA-binding proteinsIn vitro binding assaysFrontotemporal lobar degeneration-tauBinding to tau lesionsDNA-binding protein 43Tauopathy brainsHelical filamentsBrain tau pathologyTau pathologyTau lesionsSubstrate-specificBinding proteinPostmortem brain tissueCerebral amyloid angiopathyPhosphor-screen autoradiographyOff-target bindingB-amyloidAlzheimer's diseaseBinding assaysTauProtein 43