2024
Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition
Bueichekú E, Diez I, Kim C, Becker J, Koops E, Kwong K, Papp K, Salat D, Bennett D, Rentz D, Sperling R, Johnson K, Sepulcre J, Jacobs H. Spatiotemporal patterns of locus coeruleus integrity predict cortical tau and cognition. Nature Aging 2024, 4: 625-637. PMID: 38664576, PMCID: PMC11108787, DOI: 10.1038/s43587-024-00626-y.Peer-Reviewed Original ResearchConceptsTau spreadingDisease pathologyGene expression profilesTau positron emission tomography imagingTranscriptomic informationLocus coeruleusHyperphosphorylated tauAlzheimer's disease pathologyTau accumulationBiological functionsExpression profilesTau depositionGenetic featuresCortical tauAlzheimer's diseaseLocus coeruleus integrityTauAssociated with lower cognitive performanceLower cognitive performanceTransport regulationLC integrityCognitive performanceAlzheimerAllocortical regionsSpatiotemporal patterns
2023
Spatiotemporal Correlation between Amyloid and Tau Accumulations Underlies Cognitive Changes in Aging
Kim C, Diez I, Bueichekú E, Ahn S, Montal V, Sepulcre J. Spatiotemporal Correlation between Amyloid and Tau Accumulations Underlies Cognitive Changes in Aging. Journal Of Neuroscience 2023, 44: e0488232023. PMID: 38123362, PMCID: PMC10869152, DOI: 10.1523/jneurosci.0488-23.2023.Peer-Reviewed Original ResearchConceptsHarvard Aging Brain StudyCognitive changesCognitive declineAssociated with cognitive changesAssociated with early cognitive declineAging Brain StudyEarly cognitive declineTau depositionCognitive scoresBrain studiesHuman brainTau pathologyOlder adultsTau accumulationTau associationImpaired associationAD symptomsClinical trajectoryCortical patternsTauBraak stageSpatiotemporal levelsTemporal accumulationBraakFuture increases
2022
Network 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 cortexTanglesProteinApoTraitsAlzheimer
2021
Amyloid‐β and tau pathologies relate to distinctive brain dysconnectomics in autosomal‐dominant Alzheimer’s disease
Guzman‐Velez E, Diez I, Schoemaker D, Pardilla‐Delgado E, Fox‐Fuller J, Vila‐Castelar C, Baena A, Sperling R, Johnson K, Lopera F, Sepulcre J, Quiroz Y. Amyloid‐β and tau pathologies relate to distinctive brain dysconnectomics in autosomal‐dominant Alzheimer’s disease. Alzheimer's & Dementia 2021, 17 DOI: 10.1002/alz.056134.Peer-Reviewed Original ResearchAmyloid-bWeighted-degreesTau pathologyAutosomal-dominant Alzheimer's diseaseNon-carriersAutosomal-dominant ADTau burdenPredicting disease riskTau seedsPresenilin-1Tau propagationPSEN-1AD progressionSignificance thresholdAlzheimer's diseaseTauGraph-based network analysisMutation carriersTau-PETPosterior cingulate cortexMutationsConnectivity mapsGenetically-determinedResting-state fMRINetwork analysisLongitudinal predictive modeling of tau progression along the structural connectome
Yang F, Chowdhury S, Jacobs H, Sepulcre J, Wedeen V, Johnson K, Dutta J. Longitudinal predictive modeling of tau progression along the structural connectome. NeuroImage 2021, 237: 118126. PMID: 33957234, PMCID: PMC8260445, DOI: 10.1016/j.neuroimage.2021.118126.Peer-Reviewed Original ResearchConceptsHarvard Aging Brain StudyTau progressionDiffusion tensor imagingLongitudinal predictive modelsAlzheimer's Disease Neuroimaging InitiativeAlzheimer's diseaseTau PET scansPositron emission tomographyLongitudinal positron emission tomographyTau neurofibrillary tanglesAging Brain StudyTau measuresNeurofibrillary tanglesTau transmissionStructural connectivity mapsPET scansCognitive declineBrain studiesPhysiological processesTensor imagingTauStructural connectomeGoodness of model fitClosed-form solutionPrediction framework
2018
Neurogenetic contributions to amyloid beta and tau spreading in the human cortex
Sepulcre J, Grothe M, d’Oleire Uquillas F, Ortiz-Terán L, Diez I, Yang H, Jacobs H, Hanseeuw B, Li Q, El-Fakhri G, Sperling R, Johnson K. Neurogenetic contributions to amyloid beta and tau spreading in the human cortex. Nature Medicine 2018, 24: 1910-1918. PMID: 30374196, PMCID: PMC6518398, DOI: 10.1038/s41591-018-0206-4.Peer-Reviewed Original ResearchConceptsAmyloid-betaGenetic profileIdentified distinct pathwaysTau positron emission tomography imagingTau propagationTau pathwayTau spreadingGenetic backgroundAllen Human Brain AtlasDistinct pathwaysAlzheimer's diseaseTauLipid metabolismAb accumulationAdult individualsPathwayHuman Brain AtlasPathological progressionTranscriptomeMechanisms of pathological progressionBetaAmyloidProteinopathiesNeuronal circuitsApo
2017
Tau and amyloid β proteins distinctively associate to functional network changes in the aging brain
Sepulcre J, Sabuncu M, Li Q, Fakhri G, Sperling R, Johnson K. Tau and amyloid β proteins distinctively associate to functional network changes in the aging brain. Alzheimer's & Dementia 2017, 13: 1261-1269. PMID: 28366797, PMCID: PMC5623176, DOI: 10.1016/j.jalz.2017.02.011.Peer-Reviewed Original ResearchConceptsAging brainFunctional connectivityAlzheimer's disease-related pathologyCognitively normal individualsPositron emission tomography scanHyperconnected regionsFunctional network changesMisfolded tauDisease-related pathologyBrain areasEmission tomography scanAmyloid-bFunctional reorganizationB proteinHuman brainNeuronal circuitsTauBrainNeuronal functionNegative associationAmyloidCortical patternsNetwork changesElderly subjectsPositive associationPhases of Hyperconnectivity and Hypoconnectivity in the Default Mode and Salience Networks Track with Amyloid and Tau in Clinically Normal Individuals
Schultz A, Chhatwal J, Hedden T, Mormino E, Hanseeuw B, Sepulcre J, Huijbers W, LaPoint M, Buckley R, Johnson K, Sperling R. Phases of Hyperconnectivity and Hypoconnectivity in the Default Mode and Salience Networks Track with Amyloid and Tau in Clinically Normal Individuals. Journal Of Neuroscience 2017, 37: 4323-4331. PMID: 28314821, PMCID: PMC5413178, DOI: 10.1523/jneurosci.3263-16.2017.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseFunctional connectivity MRITau neurofibrillary tanglesAssociated with <i>inTau-PETNeurofibrillary tanglesAmyloid pathologyCourse of preclinical ADTau levelsTau-PET signalTau PET tracersRegional tauTau PET imagingInferior temporalPreclinical ADMolecular pathologyTauReports of associationsAmyloid PET imagingCortical association networksInferior parietal cortexAmyloidAssociated with connectivityAssociation networksPreclinical Alzheimer's disease
2016
In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain
Sepulcre J, Schultz A, Sabuncu M, Gomez-Isla T, Chhatwal J, Becker A, Sperling R, Johnson K. In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain. Journal Of Neuroscience 2016, 36: 7364-7374. PMID: 27413148, PMCID: PMC4945661, DOI: 10.1523/jneurosci.0639-16.2016.Peer-Reviewed Original ResearchConceptsHallmarks of AD pathologyAmyloid-bAlzheimer's diseaseAD pathologyHallmarks of Alzheimer's diseaseElderly human brainPositron emission tomographyBrain tissue lossHuman brainTau depositionCortical associationMatter profileCortical mantleGrey matter intensityTauSpatial patternsLocal-to-localTau positron emission tomographyCognitively normal individualsEmission tomographyCognitive symptomsHallmarksTemporal lobeNetwork analysisAssociation areas