2024
Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging
Diez I, Ortiz-Terán L, Ng T, Albers M, Marshall G, Orwig W, Kim C, Bueichekú E, Montal V, Olofsson J, Vannini P, El Fahkri G, Sperling R, Johnson K, Jacobs H, Sepulcre J. Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging. Nature Communications 2024, 15: 4809. PMID: 38844444, PMCID: PMC11156945, DOI: 10.1038/s41467-024-48462-3.Peer-Reviewed Original ResearchConceptsOlfactory systemMedial temporal lobe structuresCognitively normal older adultsOlfactory pathwayOdor identification deficitsNormal older adultsTemporal lobe structuresTau accumulationAlzheimer's diseaseIdentification deficitsGenetic vulnerabilityLobe structuresCortical systemsOlfactory circuitsAssociated with tau accumulationIdentification measuresCortical neurodegenerationOlder adultsPiB-PETTau propagationTau progressionPathological aggregationGenetic backgroundDiffusion MRIPredictive power
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
2021
College education as a modulator of the aging brain
Sepulcre J. College education as a modulator of the aging brain. Nature Aging 2021, 1: 980-981. PMID: 37118340, DOI: 10.1038/s43587-021-00131-6.Peer-Reviewed Original ResearchNetwork 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
In vivo staging of regional amyloid deposition
Grothe M, Barthel H, Sepulcre J, Dyrba M, Sabri O, Teipel S, Initiative F, Initiative A, Weiner M, Aisen P, Weiner M, Aisen P, Petersen R, Jack C, Jagust W, Trojanowki J, Toga A, Beckett L, Green R, Saykin A, Morris J, Liu E, Green R, Montine T, Petersen R, Aisen P, Gamst A, Thomas R, Donohue M, Walter S, Gessert D, Sather T, Beckett L, Harvey D, Gamst A, Donohue M, Kornak J, Jack C, Dale A, Bernstein M, Felmlee J, Fox N, Thompson P, Schuff N, Alexander G, DeCarli C, Jagust W, Bandy D, Koeppe R, Foster N, Reiman E, Chen K, Mathis C, Morris J, Cairns N, Taylor-Reinwald L, Trojanowki J, Shaw L, Lee V, Korecka M, Toga A, Crawford K, Neu S, Saykin A, Foroud T, Potkin S, Shen L, Kachaturian Z, Frank R, Snyder P, Molchan S, Kaye J, Quinn J, Lind B, Dolen S, Schneider L, Pawluczyk S, Spann B, Brewer J, Vanderswag H, Heidebrink J, Lord J, Petersen R, Johnson K, Doody R, Villanueva-Meyer J, Chowdhury M, Stern Y, Honig L, Bell K, Morris J, Ances B, Carroll M, Leon S, Mintun M, Schneider S, Marson D, Griffith R, Clark D, Grossman H, Mitsis E, Romirowsky A, deToledo-Morrell L, Shah R, Duara R, Varon D, Roberts P, Albert M, Onyike C, Kielb S, Rusinek H, de Leon M, Glodzik L, De Santi S, Doraiswamy P, Petrella J, Coleman R, Arnold S, Karlawish J, Wolk D, Smith C, Jicha G, Hardy P, Lopez O, Oakley M, Simpson D, Porsteinsson A, Goldstein B, Martin K, Makino K, Ismail M, Brand C, Mulnard R, Thai G, Mc-Adams-Ortiz C, Womack K, Mathews D, Quiceno M, Diaz-Arrastia R, King R, Weiner M, Martin-Cook K, DeVous M, Levey A, Lah J, Cellar J, Burns J, Anderson H, Swerdlow R, Apostolova L, Lu P, Bartzokis G, Silverman D, Parfitt F, Johnson H, Farlow M, Hake A, Matthews B, Herring S, van Dyck C, Carson R, MacAvoy M, Chertkow H, Bergman H, Hosein C, Black S, Stefanovic B, Caldwell C, Hsiung G, Feldman H, Mudge B, Assaly M, Kertesz A, Rogers J, Trost D, Bernick C, Munic D, Kerwin D, Mesulam M, Lipowski K, Wu C, Johnson N, Sadowsky C, Martinez W, Villena T, Turner R, Johnson K, Reynolds B, Sperling R, Johnson K, Marshall G, Frey M, Yesavage J, Taylor J, Lane B, Rosen A, Tinklenberg J, Sabbagh M, Belden C, Jacobson S, Kowall N, Killiany R, Budson A, Norbash A, Johnson P, Obisesan T, Wolday S, Bwayo S, Lerner A, Hudson L, Ogrocki P, Fletcher E, Carmichael O, Olichney J, DeCarli C, Kittur S, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Potkin S, Preda A, Nguyen D, Tariot P, Fleisher A, Reeder S, Bates V, Capote H, Rainka M, Scharre D, Kataki M, Zimmerman E, Celmins D, Brown A, Pearlson G, Blank K, Anderson K, Saykin A, Santulli R, Schwartz E, Sink K, Williamson J, Garg P, Watkins F, Ott B, Querfurth H, Tremont G, Salloway S, Malloy P, Correia S, Rosen H, Miller B, Mintzer J, Longmire C, Spicer K, Finger E, Rachinsky I, Rogers J, Kertesz A, Drost D, Pomara N, Hernando R, Sarrael A, Schultz S, Ponto L, Shim H, Smith K, Relkin N, Chaing G, Raudin L, Smith A, Fargher K, Raj B. In vivo staging of regional amyloid deposition. Neurology 2017, 89: 2031-2038. PMID: 29046362, PMCID: PMC5711511, DOI: 10.1212/wnl.0000000000004643.Peer-Reviewed Original ResearchConceptsAmyloid depositionAmyloid pathologyVivo stagingCognitive impairmentPrimary sensory-motor areasAmyloid stagesRegional amyloid depositionCSF Aβ42 levelsAlzheimer's disease dementiaSensory-motor areasAlzheimer's Disease Neuroimaging Initiative (ADNI) cohortNormal older individualsMedial temporal lobeMild cognitive impairmentAβ42 levelsDisease dementiaNeuropathologic observationsInitiative cohortAmyloid positivityTemporal lobeFull cohortCN individualsAssociative neocortexBrain regionsOlder individualsHierarchical 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 distributionThe association between tau PET and retrospective cortical thinning in clinically normal elderly
LaPoint M, Chhatwal J, Sepulcre J, Johnson K, Sperling R, Schultz A. The association between tau PET and retrospective cortical thinning in clinically normal elderly. NeuroImage 2017, 157: 612-622. PMID: 28545932, PMCID: PMC5772972, DOI: 10.1016/j.neuroimage.2017.05.049.Peer-Reviewed Original ResearchConceptsTemporal regionsCortical thinningCortical ROIsCortical thicknessRetrospective longitudinal analysisRight temporal regionAssociated with neuronal lossBaseline ageNormal cohortNeuronal lossRate of cortical thinningLeft cuneusPathologyMedial temporal regionsVolumetric ROIsReference regionAtrophyThick cross-sectionsCortical regionsBilateral parahippocampal cortexLongitudinal atrophyLongitudinal analysisLeft superior temporal sulcusCortexBrain studiesFluorodeoxyglucose metabolism associated with tau‐amyloid interaction predicts memory decline
Hanseeuw B, Betensky R, Schultz A, Papp K, Mormino E, Sepulcre J, Bark J, Cosio D, LaPoint M, Chhatwal J, Rentz D, Sperling R, Johnson K. Fluorodeoxyglucose metabolism associated with tau‐amyloid interaction predicts memory decline. Annals Of Neurology 2017, 81: 583-596. PMID: 28253546, PMCID: PMC5404378, DOI: 10.1002/ana.24910.Peer-Reviewed Original ResearchConceptsMemory declineFrontal hypometabolismHarvard Aging Brain StudyAssociated with frontal hypometabolismCourse of preclinical ADAssociated with memory lossAging Brain StudySignificant memory declinePreclinical Alzheimer's diseaseCerebral glucose metabolismAlzheimer's diseaseCingulate metabolismPosterior cingulate metabolismEntorhinal tauEntorhinal cortexPositron emission tomographyPittsburgh compound BPreclinical ADBrain studiesMemory lossImpact of amyloidOlder adultsHypometabolismAge-related tauopathyEmission tomographyTau 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 association
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
2015
Tau positron emission tomographic imaging in aging and early Alzheimer disease
Johnson K, Schultz A, Betensky R, Becker J, Sepulcre J, Rentz D, Mormino E, Chhatwal J, Amariglio R, Papp K, Marshall G, Albers M, Mauro S, Pepin L, Alverio J, Judge K, Philiossaint M, Shoup T, Yokell D, Dickerson B, Gomez-Isla T, Hyman B, Vasdev N, Sperling R. Tau positron emission tomographic imaging in aging and early Alzheimer disease. Annals Of Neurology 2015, 79: 110-119. PMID: 26505746, PMCID: PMC4738026, DOI: 10.1002/ana.24546.Peer-Reviewed Original ResearchConceptsPositron emission tomographyCognitive impairmentMild cognitive impairmentClinical impairmentAssociated with clinical impairmentInferior temporal gyrusBrain tau depositionAssociation of cognitive impairmentMild AD dementiaAD dementiaAlzheimer's diseasePositron emission tomographic imagingTau positron emission tomographyTemporal gyrusMonitoring of disease progressionEmission tomographic imagingDisease-modifying therapiesSymptomatic patientsClinically normal individualsPittsburgh compound BControl subjectsDisease progressionClinically normal controlsNormal controlsImpairment