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 increasesAssociation 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 composite
2022
Lower novelty‐related locus coeruleus function is associated with entorhinal tau‐mediated memory decline in older individuals.
Prokopiou P, Engels N, Schneider C, Schultz A, Sepulcre J, Riphagen J, Koops E, Papp K, Fakhri G, Rentz D, Sperling R, Johnson K, Jacobs H. Lower novelty‐related locus coeruleus function is associated with entorhinal tau‐mediated memory decline in older individuals. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.067706.Peer-Reviewed Original ResearchMemory declineLC activityLocus coeruleusEC tauEntorhinal cortexLC phasic activationAssociated with memory declineFace-name pairsMediation effectHarvard Aging Brain StudySteeper memory declineExposure to noveltyAssociated with tau depositionInferior temporal lobeSpatial patterns of tauAging Brain StudyPreclinical Alzheimer's diseaseCortical tau depositionTau depositionFusiform cortexMemory testInsular cortexMixed-effects analysisMediation analysisInferior temporalCorrelations between APOE4 allele and regional amyloid and tau burdens in cognitively normal older individuals
Hong Y, Kim C, Lee J, Sepulcre J. Correlations between APOE4 allele and regional amyloid and tau burdens in cognitively normal older individuals. Scientific Reports 2022, 12: 14307. PMID: 35995824, PMCID: PMC9395408, DOI: 10.1038/s41598-022-18325-2.Peer-Reviewed Original ResearchConceptsApolipoprotein epsilon 4Apolipoprotein epsilon 4 alleleAlzheimer's Disease Neuroimaging InitiativeApolipoprotein epsilon 4 carriersTau burdenAmyloid depositsAPOE4 non-carriersAssociated with amyloid depositionPresence of ApoE4 alleleCross-sectional studyRegional tau burdenAssess correlationsCognitively normal participantsIncreased amyloid burdenNormal cognitive functionCognitively normal older individualsStandardized uptake value ratioEpsilon 4AD-related biomarkersAPOE4 alleleTau depositionCortical thicknessAmyloidCarrier statusAlleles
2021
Network interdigitations of Tau and amyloid‐beta deposits define cognitive levels in aging
Kim C, Montal V, Diez I, Orwig W, Initiative A, Sepulcre J. Network interdigitations of Tau and amyloid‐beta deposits define cognitive levels in aging. Human Brain Mapping 2021, 42: 2990-3004. PMID: 33955621, PMCID: PMC8193537, DOI: 10.1002/hbm.25350.Peer-Reviewed Original ResearchConceptsCognitively normal older adultsAmyloid-betaPathological hallmarks of Alzheimer's diseaseHallmarks of Alzheimer's diseaseTau depositionPositron emission tomographyGeneral cognitive impairmentTau neurofibrillary tanglesAlzheimer's diseaseNormal older adultsOlder adultsAmyloid-beta depositionCognitive test scoresTau pathogenesisAD vulnerable areasNeurofibrillary tanglesHeteromodal areasTau accumulationCognitive changesCognitive deteriorationCognitive impairmentCognitive declinePathological hallmarkPreclinical ADCognitive level
2019
Functional and Pathological Correlates of Judgments of Learning in Cognitively Unimpaired Older Adults
Uquillas F, Jacobs H, Schultz A, Hanseeuw B, Buckley R, Sepulcre J, Pascual-Leone A, Donovan N, Johnson K, Sperling R, Vannini P. Functional and Pathological Correlates of Judgments of Learning in Cognitively Unimpaired Older Adults. Cerebral Cortex 2019, 30: 1974-1983. PMID: 31696223, PMCID: PMC7132950, DOI: 10.1093/cercor/bhz217.Peer-Reviewed Original ResearchConceptsFunctional magnetic resonance imagingCognitively unimpaired older adultsMetamemory processesMemory performanceOlder adultsMidline regionVentromedial prefrontal cortexFunctional magnetic resonance imaging signalsHarvard Aging Brain StudyJudgments of learningAging Brain StudyAlzheimer's diseaseMemory successPrefrontal cortexAssociated with overestimationNeural substratesTau pathologyBilateral hippocampiBrain studiesJOLsCohort of older adultsMagnetic resonance imagingCognitionAD dementiaTau deposition
2017
Hierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex
Sepulcre J, Grothe M, Sabuncu M, Chhatwal J, Schultz A, Hanseeuw B, Fakhri G, Sperling R, Johnson K. Hierarchical Organization of Tau and Amyloid Deposits in the Cerebral Cortex. JAMA Neurology 2017, 74: 813-820. PMID: 28558094, PMCID: PMC5710537, DOI: 10.1001/jamaneurol.2017.0263.Peer-Reviewed Original ResearchConceptsHeteromodal areasTemporal lobeHarvard Aging Brain StudyHeteromodal association regionsAging Brain StudyCognitively normal participantsElderly brainsPositron emission tomographicPrimary somatomotor cortexDistribution volume ratioAlzheimer's diseaseTau depositionStandardized uptake value ratioVisual regionsNormal participantsAb depositionSomatomotor cortexTemporal areaPittsburgh compound BCarbon 11-labeled Pittsburgh Compound BBrain studiesAssociation regionsHuman brainPathological hallmarks of Alzheimer's diseaseCortical distribution
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 areasAdvanced Neuroimaging Methods Towards Characterization of Early Stages of Alzheimer’s Disease
Sepulcre J, Masdeu J. Advanced Neuroimaging Methods Towards Characterization of Early Stages of Alzheimer’s Disease. Methods In Molecular Biology 2016, 1303: 509-519. PMID: 26235088, DOI: 10.1007/978-1-4939-2627-5_31.Peer-Reviewed Original ResearchConceptsBlood oxygen level-dependentFunctional magnetic resonance imagingAlzheimer's diseaseEarly stages of Alzheimer's diseaseOxygen level-dependentMagnetic resonance imagingStages of Alzheimer's diseaseNeurobiological changesStructural neuroimagingBrain networksBrain regionsBrains of patientsPostmortem studiesLevel-dependentNeurobiology of ADFunctional networksPostmortem dataBrainQuiet wakefulnessTau depositionResonance imagingTherapeutic interventionsNetwork propertiesNeurobiologyNeuroimaging
2015
O4‐01‐03: Entorhinal tau deposition is associated with parietal association cortex hypometabolism in clinically normal older individuals
Hanseeuw B, Schultz A, Sepulcre J, Sperling R, Johnson K. O4‐01‐03: Entorhinal tau deposition is associated with parietal association cortex hypometabolism in clinically normal older individuals. Alzheimer's & Dementia 2015, 11: p266-p267. DOI: 10.1016/j.jalz.2015.07.347.Peer-Reviewed Original ResearchTau deposition