2024
Diffusion-based Bayesian posterior distribution prediction of kinetic parameters in dynamic PET
Djebra Y, Liu X, Marin T, Tiss A, Dhaynaut M, Guehl N, Johnson K, Fakhri G, Ma C, Ouyang J. Diffusion-based Bayesian posterior distribution prediction of kinetic parameters in dynamic PET. 2024, 00: 1-1. DOI: 10.1109/nss/mic/rtsd57108.2024.10657955.Peer-Reviewed Original ResearchConditional variational autoencoderEfficient deep learning-based approachMarkov chain Monte CarloDenoising diffusion probabilistic modelDeep learning-based approachDiffusion probabilistic modelLearning-based approachApproximate posterior distributionPosterior distributionVariational autoencoderHeavy computationTau protein aggregationBayesian inferenceProbabilistic modelData-drivenStudy molecular processesBayesian posterior distributionProtein aggregationMetropolis-Hastings Markov chain Monte CarloMolecular processesAlzheimer's diseaseNeurodegenerative diseasesKinetic parametersEstimate posterior distributionsAutoencoderDiffusion Model-Based Posterior Distribution Prediction for Kinetic Parameter Estimation in Dynamic PET
Djebra Y, Liu X, Marin T, Tiss A, Dhaynaut M, Guehl N, Johnson K, Fakhri G, Ma C, Ouyang J. Diffusion Model-Based Posterior Distribution Prediction for Kinetic Parameter Estimation in Dynamic PET. 2024, 00: 1-5. DOI: 10.1109/isbi56570.2024.10635805.Peer-Reviewed Original ResearchPosterior distributions of kinetic parametersDenoising diffusion probabilistic modelHyperphosphorylated tauP-tauDiffusion probabilistic modelAlzheimer's diseaseNeurodegenerative diseasesKinetic parametersPosterior distributionInference efficiencyComputational needsEstimate kinetic parametersProbabilistic modelComputation time
2023
Locus coeruleus metabolic changes as a predictor of tau accumulation and cognitive decline
Koops E, Dutta J, Becker A, Van Egroo M, Riphagen J, Hanseeuw B, Sperling R, Fakhri G, Johnson K, Jacobs H. Locus coeruleus metabolic changes as a predictor of tau accumulation and cognitive decline. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.073715.Peer-Reviewed Original ResearchBeta-amyloidTau pathologyAlzheimer's diseaseNeuropathological hallmarks of Alzheimer's diseaseHallmarks of Alzheimer's diseaseP-tauBeta-amyloid levelsP-tau accumulationMetabolic turnoverAccumulation of p-tauMarkers of AD progressionTau formationLocus coeruleusAD pathological changesTau accumulationNeuropathological hallmarksAD progressionPhosphorylated-tauPositron emission tomographyLate stageLociPairwise analysisMetabolismPair-wise differencesFDG-PET signalHigher circulating cortisol is associated with amyloidogenesis in post‐menopausal women: The Framingham Heart Study
Salardini A, Zilli E, Himali J, Gonzales M, Himali D, Ghosh S, McGrath E, Buckley R, Satizabal C, Johnson K, Decarli C, Fakhri G, Vasan R, Seshadri S. Higher circulating cortisol is associated with amyloidogenesis in post‐menopausal women: The Framingham Heart Study. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.080594.Peer-Reviewed Original ResearchFramingham Heart StudyHeart StudyProspective cohort studyCross sectional studyPostmenopausal womenCognitively normal individualsPost-menopausal womenSectional studyAPOE4 statusAPOE4-positiveLongitudinal cohortSuperior temporal sulcusCortisol levelsMenopausal statusSecondary outcomesAlzheimer's diseaseAssociated with amyloidogenesisCortisol dysregulationBaseline plasma cortisolMorning plasma cortisolTertileFraminghamWomenAssess interactionsProgression of Alzheimer's diseaseAssociation of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology
Baril A, Kojis D, Himali J, Decarli C, Sanchez E, Johnson K, El Fakhri G, Thibault E, Yiallourou S, Himali D, Cavuoto M, Pase M, Beiser A, Seshadri S. Association of Sleep Duration and Change Over Time With Imaging Biomarkers of Cerebrovascular, Amyloid, Tau, and Neurodegenerative Pathology. Neurology 2023, 102: e207807. PMID: 38165370, PMCID: PMC10834132, DOI: 10.1212/wnl.0000000000207807.Peer-Reviewed Original ResearchConceptsHigher WMH burdenSelf-reported sleep durationLong sleep durationNeuroimaging metricsSleep durationAssociated with incident dementiaNeurodegenerative trajectoriesSleep duration categoriesNeuroimaging markersTAU outcomesIncident dementiaNeuroimagingSleep duration changesNeuroimaging testsLinear regression modelsDuration changesMRI metricsAlzheimer's diseaseAssociation 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 atrophyCognitionTau-PET abnormality as a biomarker for Alzheimer’s disease staging and early detection: a topological perspective
Ding J, Shen C, Wang Z, Yang Y, Fakhri G, Lu J, Liang D, Zheng H, Zhou Y, Sun T, Study F. Tau-PET abnormality as a biomarker for Alzheimer’s disease staging and early detection: a topological perspective. Cerebral Cortex 2023, 33: 10649-10659. PMID: 37653600, DOI: 10.1093/cercor/bhad312.Peer-Reviewed Original ResearchConceptsStandardized uptake value ratioMild cognitive impairmentBrain regionsCognitive impairmentPositron emission tomographyMedial temporal lobeAlzheimer's diseaseVisual-related regionsTopological perspectiveTau positron emission tomographyMode networkTau PET imagingTopological featuresIndependent data cohortsTemporal lobeConnection strengthExtract topological featuresTau networksAbnormal networkProgression of Alzheimer's diseaseAbnormal protein accumulation
2022
Longitudinal hippocampal atrophy is associated with cognitive decline independently of amyloid and tau in neocortex
Hanseeuw B, Jacobs H, Schultz A, Buckley R, Properzi M, Becker A, Farrell M, Sanchez J, Papp K, Yang H, Chhatwal J, Price J, Fakhri G, Rentz D, Sperling R, Johnson K. Longitudinal hippocampal atrophy is associated with cognitive decline independently of amyloid and tau in neocortex. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.069271.Peer-Reviewed Original ResearchNetwork Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes
Montal V, Diez I, Kim C, Orwig W, Bueichekú E, Gutiérrez-Zúñiga R, Bejanin A, Pegueroles J, Dols-Icardo O, Vannini P, El-Fakhri G, Johnson K, Sperling R, Fortea J, Sepulcre J. Network Tau spreading is vulnerable to the expression gradients of APOE and glutamatergic-related genes. Science Translational Medicine 2022, 14: eabn7273. PMID: 35895837, PMCID: PMC9942690, DOI: 10.1126/scitranslmed.abn7273.Peer-Reviewed Original ResearchConceptsTau spreadingIntracellular accumulation of tau proteinAccumulation of tau proteinAlzheimer's diseasePathological tau accumulationGenetic gradientGenetic dataTau proteinNeurofibrillary tanglesSynaptic genesTau accumulationGenetic traitsGenesDrug development strategiesExpression gradientIntracellular accumulationTauExpressionCognitively normal older participantsHuman brain cortexTanglesProteinApoTraitsAlzheimerLower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals
Prokopiou P, Engels-Domínguez N, Papp K, Scott M, Schultz A, Schneider C, Farrell M, Buckley R, Quiroz Y, El Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals. Nature Communications 2022, 13: 1571. PMID: 35322012, PMCID: PMC8943159, DOI: 10.1038/s41467-022-28986-2.Peer-Reviewed Original ResearchConceptsCognitive declineLC activityLC-FCFunctional connectivityLocus coeruleusAssociated with altered neuronal activityNeuronal activityFace-name paradigmAD-related cognitive declineHuman imaging researchIn vivo neuronal activityLongitudinal cognitive dataAssociated with cognitive declineBeta-amyloid-PETIndividuals at-riskAlzheimer's diseaseCognitively unimpaired older individualsBeta-amyloidSubcortical regionsFunctional MRICognitive dataNeurofibrillary tauImaging researchHippocampusCognitionImpact 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
Toward noninvasive brain stimulation 2.0 in Alzheimer’s disease
Menardi A, Rossi S, Koch G, Hampel H, Vergallo A, Nitsche M, Stern Y, Borroni B, Cappa S, Cotelli M, Ruffini G, El-Fakhri G, Rossini P, Dickerson B, Antal A, Babiloni C, Lefaucheur J, Dubois B, Deco G, Ziemann U, Pascual-Leone A, Santarnecchi E. Toward noninvasive brain stimulation 2.0 in Alzheimer’s disease. Ageing Research Reviews 2021, 75: 101555. PMID: 34973457, PMCID: PMC8858588, DOI: 10.1016/j.arr.2021.101555.Peer-Reviewed Original ResearchLocus coeruleus integrity as a proxy of initial tau burden: in vivo versus ex vivo observations
Jacobs H, Becker A, Kwong K, Engels N, Prokopiou P, Papp K, Properzi M, Hampton O, Sanchez J, Rentz D, Fakhri G, Normandin M, Bennett D, Sperling R, Johnson K. Locus coeruleus integrity as a proxy of initial tau burden: in vivo versus ex vivo observations. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.056391.Peer-Reviewed Original ResearchHarvard Aging Brain StudyMini-Mental State ExaminationLC integrityLocus coeruleusMini-Mental State Examination scoreNeuronal densityTangle densityLocus coeruleus integrityAging Brain StudyTau pathologyAlzheimer's diseaseAD-related processesVertex-wiseTemporal regionsBraak stageLC measurementsMini-MentalMCI/AD patientsState ExaminationBrain studiesPiB-PET imagingTau-PETPET measurementsPiB-PETTangle burdenIn vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline
Jacobs H, Becker J, Kwong K, Engels-Domínguez N, Prokopiou P, Papp K, Properzi M, Hampton O, d'Oleire Uquillas F, Sanchez J, Rentz D, El Fakhri G, Normandin M, Price J, Bennett D, Sperling R, Johnson K. In vivo and neuropathology data support locus coeruleus integrity as indicator of Alzheimer’s disease pathology and cognitive decline. Science Translational Medicine 2021, 13: eabj2511. PMID: 34550726, PMCID: PMC8641759, DOI: 10.1126/scitranslmed.abj2511.Peer-Reviewed Original ResearchConceptsLC integrityLongitudinal cognitive measuresCognitive measuresLocus coeruleusIndicators of Alzheimer's disease pathologyLocus coeruleus integrityMedial temporal lobeTangle densityRush Memory and Aging ProjectBraak stageMemory and Aging ProjectHyperphosphorylated tau aggregatesAlzheimer's diseaseB-amyloidAD-related processesMemory declineCognitive dysfunctionDisease pathologyCognitive trajectoriesTemporal lobeLC neuronsPostmortem correlationsCognitive declineEntorhinal cortexPreclinical ADSynthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2
Yuan G, Guehl N, Zheng B, Qu X, Moon S, Dhaynaut M, Shoup T, Afshar S, Kang H, Zhang Z, El Fakhri G, Normandin M, Brownell A. Synthesis and Characterization of [18F]JNJ-46356479 as the First 18F-Labeled PET Imaging Ligand for Metabotropic Glutamate Receptor 2. Molecular Imaging And Biology 2021, 23: 527-536. PMID: 33559035, PMCID: PMC8277681, DOI: 10.1007/s11307-021-01586-0.Peer-Reviewed Original ResearchConceptsNon-human primatesIn vivo PET imaging studiesNucleus accumbensGlutamate receptor 2PET imaging ligandsImaging ligandsParietal cortexBrain regionsPET imaging studiesPET radioligandIn vivo PET imaging experimentsVolume of distributionMGluR2C57BL/6 J micePET imaging experimentsPET studiesBrainSprague-Dawley ratsAlzheimer's diseaseBrain permeabilityPre-treatment studyImaging studiesDisordersRat studiesReversible kineticsThe 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 ResearchConceptsPositron 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
Tracking the origin of tau spread in the brain
Jacobs H, Becker A, Kwong K, Uquillas F, Papp K, Properzi M, Rentz D, Fakhri G, Sperling R, Johnson K. Tracking the origin of tau spread in the brain. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.037501.Peer-Reviewed Original ResearchEntorhinal cortexMemory declineLocus coeruleusHarvard Aging Brain StudyPosterior cingulate cortexProspective memory declineAD-related cognitive declineMedial temporal lobeAging Brain StudyTau spreadingAlzheimer's diseaseCingulate cortexLimbic regionsNeuropsychological assessmentCingulate regionsTau PET imagingLC integrityCognitive changesTau accumulationMediation analysisTemporal lobeEntorhinal tauIncreased ABCognitive declineBrain studiesAttenuation correction using deep Learning and integrated UTE/multi-echo Dixon sequence: evaluation in amyloid and tau PET imaging
Gong K, Han P, Johnson K, El Fakhri G, Ma C, Li Q. Attenuation correction using deep Learning and integrated UTE/multi-echo Dixon sequence: evaluation in amyloid and tau PET imaging. European Journal Of Nuclear Medicine And Molecular Imaging 2020, 48: 1351-1361. PMID: 33108475, PMCID: PMC8411350, DOI: 10.1007/s00259-020-05061-w.Peer-Reviewed Original ResearchConceptsAttenuation correctionResultsThe Dice coefficientPseudo-CT imagesMR-based AC methodsAccurate ACAC accuracyPET imagingDice coefficientQuantitative accuracyAtlas methodAC methodGradient echoNear verticesTau imagingTau PET imagingAlzheimer's diseaseUltrashortCorrectionTau pathologyRapid acquisitionDeep learning methodsMonitoring of Alzheimer’s diseasePET/MRAmyloid
2019
Visual cognition in non-amnestic Alzheimer's disease: Relations to tau, amyloid, and cortical atrophy
Putcha D, Brickhouse M, Touroutoglou A, Collins J, Quimby M, Wong B, Eldaief M, Schultz A, Fakhri G, Johnson K, Dickerson B, McGinnis S. Visual cognition in non-amnestic Alzheimer's disease: Relations to tau, amyloid, and cortical atrophy. NeuroImage Clinical 2019, 23: 101889. PMID: 31200149, PMCID: PMC6562373, DOI: 10.1016/j.nicl.2019.101889.Peer-Reviewed Original ResearchConceptsVisual cognitive testsNeuropsychological batteryAssociated with tauVariant of ADCortical atrophyCognitive testsLogopenic variant primary progressive aphasiaVariant primary progressive aphasiaMagnetic resonance imagingPrimary progressive aphasiaStructural magnetic resonance imagingVentral occipitotemporal cortexSuperior parietal cortexCognitive test performanceVisual cognitive dysfunctionCognitive task performanceNon-amnestic variantsSpatial patterns of tauAlzheimer's diseasePosterior cortical dysfunctionVisual cortical regionsOccipital association corticesAmyloid PETAmyloid-positive patientsPosterior cortical atrophyAutoradiography 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