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 compositeImpact of motion correction on [18F]-MK6240 tau PET imaging
Tiss A, Marin T, Chemli Y, Spangler-Bickell M, Gong K, Lois C, Petibon Y, Landes V, Grogg K, Normandin M, Becker A, Thibault E, Johnson K, Fakhri G, Ouyang J. Impact of motion correction on [18F]-MK6240 tau PET imaging. Physics In Medicine And Biology 2023, 68: 105015. PMID: 37116511, PMCID: PMC10278956, DOI: 10.1088/1361-6560/acd161.Peer-Reviewed Original ResearchConceptsMotion correctionPET quantitationImpact of motion correctionList-mode reconstructionMotion correction methodList-mode dataMotion-corrected imagesEffect of motion correctionVoxel displacementsPhantom experimentsOptical tracking dataLong acquisitionBrain PET scansSlow motionImage qualityPET imagingPositron emission tomographyCorrectionMotionCorrection methodRates of tau accumulationHead motionMotion metricsPhantomPositron
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
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 courseAutoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue
Aguero C, Dhaynaut M, Normandin M, Amaral A, Guehl N, Neelamegam R, Marquie M, Johnson K, El Fakhri G, Frosch M, Gomez-Isla T. Autoradiography validation of novel tau PET tracer [F-18]-MK-6240 on human postmortem brain tissue. Acta Neuropathologica Communications 2019, 7: 37. PMID: 30857558, PMCID: PMC6410510, DOI: 10.1186/s40478-019-0686-6.Peer-Reviewed Original ResearchConceptsIn vivo detection of neurofibrillary tanglesNeurofibrillary tanglesDetection of neurofibrillary tanglesAlzheimer's diseaseTDP-43Binds to neurofibrillary tanglesFrontotemporal lobar degeneration-tauOff-target bindingDNA-binding protein 43Binding patternsNon-Alzheimer tauopathiesHuman postmortem brain tissueTau aggregationPostmortem brain tissueBinding signalBinding targetsCerebral amyloid angiopathyIn vivo detectionB-amyloidNeurodegenerative diseasesHuman brain tissueTauTau positron emission tomographyBindingMK-6240
2018
[18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM
Verwer E, Kavanagh T, Mischler W, Feng Y, Takahashi K, Wang S, Shoup T, Neelamegam R, Yang J, Guehl N, Ran C, Massefski W, Cui Y, El-Chemaly S, Sadow P, Oldham W, Kijewski M, Fakhri G, Normandin M, Priolo C. [18F]Fluorocholine and [18F]Fluoroacetate PET as Imaging Biomarkers to Assess Phosphatidylcholine and Mitochondrial Metabolism in Preclinical Models of TSC and LAM. Clinical Cancer Research 2018, 24: 5925-5938. PMID: 30054282, PMCID: PMC6816044, DOI: 10.1158/1078-0432.ccr-17-3693.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnimalsBiomarkersCholineDisease Models, AnimalFemaleFluoroacetatesHeterograftsHumansImage Processing, Computer-AssistedImmunohistochemistryLipid MetabolismLymphangioleiomyomatosisMaleMiceMice, TransgenicMitochondriaOxygen ConsumptionPhosphatidylcholinesPositron-Emission TomographyRatsTuberous SclerosisConceptsTuberous sclerosis complexMetabolic imaging biomarkersPreclinical modelsImaging biomarkersTSC2-deficient cellsStandardized uptake valueTuberous sclerosis complex manifestationsModels of tuberous sclerosis complexAutosomal dominant disorderPotential clinical interestBenign tumorsOvariectomized miceUptake valueSubcutaneous tumorsPreclinical studiesPulmonary nodulesCystic destructionLymphangioleiomyomatosisDominant disorderProliferative lesionsInactivating mutationsTumorMetabolic reprogrammingNeurocognitive impairmentPET imaging
2017
Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case
Marquié M, Verwer E, Meltzer A, Kim S, Agüero C, Gonzalez J, Makaretz S, Siao Tick Chong M, Ramanan P, Amaral A, Normandin M, Vanderburg C, Gomperts S, Johnson K, Frosch M, Gómez-Isla T. Lessons learned about [F-18]-AV-1451 off-target binding from an autopsy-confirmed Parkinson’s case. Acta Neuropathologica Communications 2017, 5: 75. PMID: 29047416, PMCID: PMC5648451, DOI: 10.1186/s40478-017-0482-0.Peer-Reviewed Original ResearchConceptsPositron emission tomographyBasal gangliaBinding to neuromelaninPositron emission tomography studiesDementia of AD typeInferior temporal cortexParkinson's diseaseTau pathologyPositron emission tomography scanAlzheimer's diseaseMild cognitive impairmentTemporal cortexAutoradiographic bindingBrain regionsNeurofibrillary tau pathologyOccipital cortexPositron emission tomography signalCognitive impairmentPostmortem materialEntorhinal cortexSubstantia nigraParenchymal hemorrhagePD diagnosisAutoradiography experimentsChoroid plexus[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 evaluation
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 43Imaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences
Normandin MD, Zheng MQ, Lin KS, Mason NS, Lin SF, Ropchan J, Labaree D, Henry S, Williams WA, Carson RE, Neumeister A, Huang Y. Imaging the Cannabinoid CB1 Receptor in Humans with [11C] OMAR: Assessment of Kinetic Analysis Methods, Test–Retest Reproducibility, and Gender Differences. Cerebrovascular And Brain Metabolism Reviews 2015, 35: 1313-1322. PMID: 25833345, PMCID: PMC4528005, DOI: 10.1038/jcbfm.2015.46.Peer-Reviewed Original ResearchConceptsTest-retest reliabilityCannabinoid type 1 receptorType 1 receptorCannabinoid CB1 receptorsPositron emission tomography (PET) imagingTest-retest reproducibilityEmission Tomography ImagingGender differencesTwo-tissue compartment modelCerebral uptakePresent studyCB1 receptorsCB1R availabilityInjected doseVascular componentBody weightReceptor availabilityNeuropsychiatric disordersMultilinear analysis methodRegional volumesReceptor bindingTomography imagingParent fractionOne-tissueHuman subjects