2025
A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease
de Geus M, Nairn A, Arnold S, Carlyle B. A compilation of reported alterations in the cerebrospinal fluid proteome in Alzheimer's disease. Brain Communications 2025, 7: fcaf202. PMID: 40491829, PMCID: PMC12146149, DOI: 10.1093/braincomms/fcaf202.Peer-Reviewed Original ResearchDifferentially expressed proteinsExpressed proteinsAlzheimer's diseaseReactive oxygen speciesFunctional enrichment analysisHeterogeneity of Alzheimer's diseaseAmyloid-bAlzheimer's disease cerebrospinal fluidAlzheimer's disease pathologyAlzheimer's disease datasetProteomic dataProteomic landscapeTau accumulationEnrichment analysisMetabolic regulationOmics studiesCerebrospinal fluid proteomeProtein changesProteinNeurodegenerative disordersDiverse mechanismsSynaptic signal processingDisease pathologyGlutathione metabolismOxygen species
2024
Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum
Trelle A, Young C, Vossler H, Benitez J, Cody K, Mendiola J, Swarovski M, Le Guen Y, Feinstein I, Butler R, Channappa D, Romero A, Park J, Shahid‐Besanti M, Corso N, Chau K, Smith A, Skylar‐Scott I, Yutsis M, Fredericks C, Tian L, Younes K, Kerchner G, Deutsch G, Davidzon G, Sha S, Henderson V, Longo F, Greicius M, Wyss‐Coray T, Andreasson K, Poston K, Wagner A, Mormino E, Wilson E. Plasma Aβ42/Aβ40 is sensitive to early cerebral amyloid accumulation and predicts risk of cognitive decline across the Alzheimer's disease spectrum. Alzheimer's & Dementia 2024, 21: e14442. PMID: 39713875, PMCID: PMC11848181, DOI: 10.1002/alz.14442.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseCognitive declinePositron emission tomographyAmyloid-betaTau accumulationAmyloid positivityHippocampal-dependent memoryAlzheimer's disease spectrumAmyloidAmyloid accumulationTau burdenAb accumulationRisk of cognitive declineSensitive to memoryTau positron emission tomographyAlzheimer's Disease Research CenterPredicting cognitive declineAlzheimerTauScalable biomarkersAD continuumCerebral amyloid accumulationCross-sectional associationsCI individualsAccumulationAD Pathology Spreading Detection Using Directional Motifs in Brain Connectomes
Bueichekú E, Diez I, Úbeda A, Kim C, Jacobs H, Sepulcre J. AD Pathology Spreading Detection Using Directional Motifs in Brain Connectomes. Alzheimer's & Dementia 2024, 20: e088834. PMCID: PMC11710655, DOI: 10.1002/alz.088834.Peer-Reviewed Original ResearchTau progressionAlzheimer's diseaseNetwork motifsProgression of tau pathologyContext of ADFeed-forward loopToxic tauTau propagationTau proteinTau pathologyTau accumulationProtein spreadingMotifMotif networkEmergence of cognitive declineMedial prefrontal regionsAmyloid accumulationTauCharacteristics of pathologyMild cognitive impairmentAlzheimer's Disease Neuroimaging InitiativePrefrontal regionsTau PET dataBrain systemsClinical ADAPOE4 moderates the association between cerebral small vessel disease and cortical tau accumulation in midlife
Espinoza L, Scott M, Beiser A, Banh A, Philip V, Ghosh S, Thibault E, Maillard P, Decarli C, Fakhri G, Johnson K, Seshadri S, Satizabal C. APOE4 moderates the association between cerebral small vessel disease and cortical tau accumulation in midlife. Alzheimer's & Dementia 2024, 20: e091824. PMCID: PMC11714429, DOI: 10.1002/alz.091824.Peer-Reviewed Original ResearchAPOE-e4 genotypeAPOE-e4APOE-e4 carriersBiomarkers of cerebral small vessel diseaseIncreased risk of ADSignificant associationFramingham Heart StudyThird Generation cohortsRegional tauCerebral small vessel diseaseCognitively healthy participantsRisk of ADMiddle-aged adultsBorderline significant associationCardiovascular risk factorsSmall vessel diseaseDementia onsetNo significant associationHeart StudyPotential confoundersAlzheimer's diseaseLinear regression modelsE4 genotypeTau accumulationIncreased riskExamining early cerebral amyloid beta and tau accumulation in association with cognition in a predominantly middle‐aged cohort
Gonzales M, O’Donnell A, Ghosh S, Thibault E, Tanner J, Satizabal C, Decarli C, Fakhri G, Johnson K, Beiser A, Seshadri S, Pase M. Examining early cerebral amyloid beta and tau accumulation in association with cognition in a predominantly middle‐aged cohort. Alzheimer's & Dementia 2024, 20: e087431. PMCID: PMC11716433, DOI: 10.1002/alz.087431.Peer-Reviewed Original ResearchStratified analysisPoorer visuospatial functionFramingham Heart StudyTau positron emission tomographyPositron emission tomographyMiddle-aged cohortApolipoprotein E4 statusCommunity-based cohortTau accumulationAssociated with cognitive declineVisuospatial functionLow cognitive reserveAssociated with cognitionAmyloid-betaHeart StudyOlder adultsE4 statusLinear regression modelsCerebral amyloid-betaPoor cognitionMeasures of ABCognitive AssessmentCollege degreeCognitive reserveMidlifePlasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at 18F-SynVesT-1 Brain PET Imaging.
Wu J, Li B, Wang J, Huang Q, Chen X, You Z, He K, Guo Q, Li S, Huang Y, Guo T, Dai W, Xiang W, Chen W, Yang D, Zhao J, Guan Y, Xie F. Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at 18F-SynVesT-1 Brain PET Imaging. Radiology 2024, 313: e233019. PMID: 39560478, PMCID: PMC11605102, DOI: 10.1148/radiol.233019.Peer-Reviewed Original ResearchConceptsP-tau-181Alzheimer's diseaseAD-related pathologyAmyloid-bPhosphor-tauTau pathologySynaptic densityTau accumulationSynaptic lossTauTau-PETDecreased synaptic densityGlial fibrillary acidic proteinPlasma glial fibrillary acidic proteinCortical thicknessAcidic proteinFibrillary acidic proteinRuijin HospitalProspective studyRelationship of plasmaBlood assayBlood markersPET/MRIBrain PET imagingPET imagingTau 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 powerSpatiotemporal 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
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 signalSpatiotemporal Assessment of Locus Coeruleus Integrity Predicting Cortical Tau and Cognition
Bueichekú E, Diez I, Kim C, Becker A, Koops E, Kwong K, Papp K, Salat D, Bennett D, Rentz D, Sperling R, Johnson K, Sepulcre J, Jacobs H. Spatiotemporal Assessment of Locus Coeruleus Integrity Predicting Cortical Tau and Cognition. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079747.Peer-Reviewed Original ResearchLC integrityLocus coeruleusLower cognitive performanceLongitudinal tau accumulationCognitive performanceEmergence of cognitive declineAssociated with lower cognitive performanceTemporal cortex areasIn vivo neuroimaging dataTau accumulationTau progressionCortical tau depositionAlzheimer's diseaseNeuroimaging studiesMTL structuresNeuroimaging dataAD-related pathologyCognitive declineCortex areaPartial correlationMisfolded tau proteinContext of ADGLM analysisSites of tauLipid biosynthetic processRelationship between loss of awareness of cognitive decline and tau pathology in the Alzheimer’s disease spectrum: modulatory role of resting‐state functional connectivity
Cacciamani F, Gagliardi G, Mimmack K, Qiao K, Bueichekú E, Marshall G, Sepulcre J, Diez I, Vannini P. Relationship between loss of awareness of cognitive decline and tau pathology in the Alzheimer’s disease spectrum: modulatory role of resting‐state functional connectivity. Alzheimer's & Dementia 2023, 19 DOI: 10.1002/alz.079806.Peer-Reviewed Original ResearchAwareness of cognitive declineResting-state functional connectivityLinear regression modelsSelf-referential networkHigher tau burdenFunctional connectivityCognitive declineRegression modelsTau accumulationAlzheimer's diseaseImpaired resting-state functional connectivityAlzheimer's disease spectrumResting-state fMRI dataAssociated with tau accumulationDorsal attention networkReduced awarenessWithin-network connectivityModulatory roleLow awarenessTau burdenEffects of tauCognitive function indicesTau interactionsSalience networkTau pathologySpatiotemporal 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 increasesSex-specific modulation of amyloid-β on tau phosphorylation underlies faster tangle accumulation in females
Wang Y, Therriault J, Servaes S, Tissot C, Rahmouni N, Macedo A, Fernandez-Arias J, Mathotaarachchi S, Benedet A, Stevenson J, Ashton N, Lussier F, Pascoal T, Zetterberg H, Rajah M, Blennow K, Gauthier S, Rosa-Neto P, 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, Perrin R, Shaw L, Khachaturian Z, Carrillo M, Potter W, Barnes L, Bernard M, Hsiao J, Jackson J, Masliah E, Masterman D, Okonkwo O, Perrin R, Ryan L, Silverberg N, Fleisher A, Weiner M, Sacrey D, Fockler J, Conti C, Veitch D, Neuhaus J, Jin C, Nosheny R, Ashford M, Flenniken D, Kormos A, Green R, Montine T, Conti C, Petersen R, Aisen P, Rafii M, Raman R, Jimenez G, Donohue M, Gessert D, Salazar J, Zimmerman C, Cabrera Y, Walter S, Miller G, Coker G, Clanton T, Hergesheimer L, Smith S, Adegoke O, Mahboubi P, Moore S, Pizzola J, Shaffer E, Sloan B, Beckett L, Harvey D, Donohue M, Jack C, Forghanian-Arani A, Borowski B, Ward C, Schwarz C, Jones D, Gunter J, Kantarci K, Senjem M, Vemuri P, Reid R, Fox N, Malone I, Thompson P, Thomopoulos S, Nir T, Jahanshad N, DeCarli C, Knaack A, Fletcher E, Harvey D, Tosun-Turgut D, Chen S, Choe M, Crawford K, Yushkevich P, Das S, Jagust W, Koeppe R, Reiman E, Chen K, Mathis C, Landau S, Morris J, Perrin R, Cairns N, Householder E, Franklin E, Bernhardt H, Taylor-Reinwald L, Shaw L, Trojanowki J, Korecka M, Figurski M, Toga A, Neu S, Saykin A, Nho K, Risacher S, Apostolova L, Shen L, Foroud T, Nudelman K, Faber K, Wilmes K, Weiner M, Thal L, Khachaturian Z, Hsiao J, Silbert L, Lind B, Crissey R, Kaye J, Carter R, Dolen S, Quinn J, Schneider L, Pawluczyk S, Becerra M, Teodoro L, Dagerman K, Spann B, Brewer J, Vanderswag H, Fleisher A, Ziolkowski J, Heidebrink J, Zbizek-Nulph L, Lord J, Zbizek-Nulph L, Petersen R, Mason S, Albers C, Knopman D, Johnson K, Villanueva-Meyer J, Pavlik V, Pacini N, Lamb A, Kass J, Doody R, Shibley V, Chowdhury M, Rountree S, Dang M, Stern Y, Honig L, Mintz A, Ances B, Morris J, Winkfield D, Carroll M, Stobbs-Cucchi G, Oliver A, Mintun M, Schneider S, Geldmacher D, Love M, Griffith R, Clark D, Brockington J, Marson D, Grossman H, Goldstein M, Greenberg J, Mitsis E, Shah R, Lamar M, Samuels P, Duara R, Greig-Custo M, Rodriguez R, Albert M, Onyike C, Farrington L, Rudow S, Brichko R, Kielb S, Smith A, Raj B, Fargher K, Sadowski M, Wisniewski T, Shulman M, Faustin A, Rao J, Castro K, Ulysse A, Chen S, Sheikh M, Singleton-Garvin J, Doraiswamy P, Petrella J, James O, Wong T, Borges-Neto S, Karlawish J, Wolk D, Vaishnavi S, Clark C, Arnold S, Smith C, Jicha G, El Khouli R, Raslau F, Lopez O, Oakley M, Simpson D, Porsteinsson A, Martin K, Kowalski N, Keltz M, Goldstein B, Makino K, Ismail M, Brand C, Thai G, Pierce A, Yanez B, Sosa E, Witbracht M, Kelley B, Nguyen T, Womack K, Mathews D, Quiceno M, Levey A, Lah J, Hajjar I, Cellar J, Burns J, Swerdlow R, Brooks W, Daniel Silverman H, Kremen S, Apostolova L, Tingus K, Lu P, Bartzokis G, Woo E, Teng E, Graff-Radford N, Parfitt F, Poki-Walker K, Farlow M, Hake A, Matthews B, Brosch J, Herring S, van Dyck C, Mecca A, Mecca A, Good S, MacAvoy M, Carson R, Varma P, Chertkow H, Vaitekunis S, Hosein C, Black S, Stefanovic B, Heyn C, Hsiung G, Kim E, Mudge B, Sossi V, Feldman H, Assaly M, Finger E, Pasternak S, Rachinsky I, Kertesz A, Drost D, Rogers J, Grant I, Muse B, Rogalski E, Robson J, Mesulam M, Kerwin D, Wu C, Johnson N, Lipowski K, Weintraub S, Bonakdarpour B, Pomara N, Hernando R, Sarrael A, Rosen H, Miller B, Perry D, Turner R, Johnson K, Reynolds B, MCCann K, Poe J, Sperling R, Johnson K, Marshall G, Yesavage J, Taylor J, Chao S, Coleman J, White J, Lane B, Rosen A, Tinklenberg J, Belden C, Atri A, Spann B, Clark K, Zamrini E, Sabbagh M, Killiany R, Stern R, Mez J, Kowall N, Budson A, Obisesan T, Ntekim O, Wolday S, Khan J, Nwulia E, Nadarajah S, Lerner A, Ogrocki P, Tatsuoka C, Fatica P, Fletcher E, Maillard P, Olichney J, DeCarli C, Carmichael O, Bates V, Capote H, Rainka M, Borrie M, Lee T, Bartha R, Johnson S, Asthana S, Carlsson C, Perrin A, Burke A, Scharre D, Kataki M, Tarawneh R, Kelley B, Hart D, Zimmerman E, Celmins D, Miller D, Ponto L, Smith K, Koleva H, Shim H, Nam K, Schultz S, Williamson J, Craft S, Cleveland J, Yang M, Sink K, Ott B, Drake J, Tremont G, Daiello L, Drake J, Sabbagh M, Ritter A, Bernick C, Munic D, Mintz A, O’Connelll A, Mintzer J, Wiliams A, Masdeu J, Shi J, Garcia A, Sabbagh M, Newhouse P, Potkin S, Salloway S, Malloy P, Correia S, Kittur S, Pearlson G, Blank K, Anderson K, Flashman L, Seltzer M, Hynes M, Santulli R, Relkin N, Chiang G, Lin M, Ravdin L, Lee A, Weiner M, Aisen P, Weiner M, Aisen P, Petersen R, Green R, Harvey D, Jack C, Jagust W, Morris J, Saykin A, Shaw L, Toga A, Trojanowki J, Neylan T, Grafman J, Green R, Montine T, Weiner M, Petersen R, Aisen P, Jimenez G, Donohue M, Gessert D, Salazar J, Zimmerman C, Walter S, Adegoke O, Mahboubi P, Danowski S, Coker G, Clanton T, Pizzola J, Shaffer E, Nguyen-Barrera C, Neylan T, Hayes J, Finley S, Harvey D, Donohue M, Jack C, Bernstein M, Borowski B, Gunter J, Senjem M, Kantarci K, Ward C, Chen S, Landau S, Koeppe R, Foster N, Reiman E, Chen K, Morris J, Perrin R, Franklin E, Shaw L, Trojanowki J, Korecka M, Figurski M, Toga A, Crawford K, Neu S, Saykin A, Foroud T, Potkin S, Shen L, Faber K, Kim S, Nho K, Wilmes K, Schneider L, Teodoro L, Dagerman K, Spann B, Brewer J, Vanderswag H, Fleisher A, Stern Y, Honig L, Mintz A, Shah R, Sood A, Blanchard K, Duara R, Varon D, Greig M, Doraiswamy P, Borges-Neto S, Wong T, Porsteinsson A, Thai G, Pierce A, Reist C, Yanez B, Sosa E, Witbracht M, Sadowsky C, Martinez W, Villena T, Rosen H, Perry D, Turner R, Johnson K, Reynolds B, MCCann K, Poe J, Sperling R, Johnson K, Marshall G, Belden C, Atri A, Spann B, Clark K, Zamrini E, Sabbagh M, Obisesan T, Ntekim O, Wolday S, Nwulia E, Nadarajah S, Johnson S, Asthana S, Carlsson C, Peskind E, Petrie E, Li G, Yesavage J, Taylor J, Chao S, Coleman J, White J, Lane B, Rosen A, Tinklenberg J, Lin M, Chiang G, Ravdin L, Relkin N, O’Connelll A, Mintzer J, Wiliams A, Mackin S, Aisen P, Raman R, Jimenez-Maggiora G, Donohue M, Gessert D, Salazar J, Zimmerman C, Walter S, Adegoke O, Mahboubi P, Mackin S, Weiner M, Aisen P, Raman R, Jack C, Landau S, Saykin A, Toga A, DeCarli C, Koeppe R, Green R, Drake E, Weiner M, Aisen P, Raman R, Donohue M, Mackin S, Nelson C, Bickford D, Butters M, Zmuda M, Jack C, Bernstein M, Borowski B, Gunter J, Senjem M, Kantarci K, Ward C, Reyes D, Koeppe R, Landau S, Toga A, Neu S, Saykin A, Foroud T, Faber K, Nho K, Nudelman K, Mackin S, Rosen H, Nelson C, Bickford D, Au Y, Scherer K, Catalinotto D, Stark S, Ong E, Fernandez D, Butters M, Zmuda M, Lopez O, Oakley M, Simpson D. Sex-specific modulation of amyloid-β on tau phosphorylation underlies faster tangle accumulation in females. Brain 2023, 147: 1497-1510. PMID: 37988283, PMCID: PMC10994548, DOI: 10.1093/brain/awad397.Peer-Reviewed Original ResearchConceptsTau phosphorylationTau tangle formationNeurofibrillary tanglesAmyloid-bTangle formationSpread of tau aggregatesSex-specific modulationTangle accumulationP-tauLoad of neurofibrillary tanglesAlzheimer's diseaseUpstream pathological eventTau aggregationTau tanglesNeurofibrillary tangle accumulationTau progressionTau accumulationPhosphorylated-tauPhosphorylationCSF p-tau181TanglesTauSex-specific mannerP-tau181P-tau181 concentrationsNeuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein
Stoner A, Fu L, Nicholson L, Zheng C, Toyonaga T, Spurrier J, Laird W, Cai Z, Strittmatter S. Neuronal transcriptome, tau and synapse loss in Alzheimer’s knock-in mice require prion protein. Alzheimer's Research & Therapy 2023, 15: 201. PMID: 37968719, PMCID: PMC10647125, DOI: 10.1186/s13195-023-01345-z.Peer-Reviewed Original ResearchConceptsSynapse lossDKI miceTau accumulationBrain immune activationNeural network dysfunctionPhospho-tau accumulationAccumulation of tauNeuronal genesInflammatory markersAD miceAβ levelsPrion proteinDystrophic neuritesImmune activationTau pathologyNeuronal gene expressionAmyloid-β OligomersGliotic reactionNetwork dysfunctionBehavioral deficitsSynaptic failureAD modelMemory impairmentAlzheimer's diseaseFunction of ageCortical microstructural changes predict tau accumulation and episodic memory decline in older adults harboring amyloid
Gagliardi G, Rodriguez-Vieitez E, Montal V, Sepulcre J, Diez I, Lois C, Hanseeuw B, Schultz A, Properzi M, Papp K, Marshall G, Fortea J, Johnson K, Sperling R, Vannini P. Cortical microstructural changes predict tau accumulation and episodic memory decline in older adults harboring amyloid. Communications Medicine 2023, 3: 106. PMID: 37528163, PMCID: PMC10394044, DOI: 10.1038/s43856-023-00324-7.Peer-Reviewed Original ResearchLogical Memory delayed recallEpisodic memory declineMemory declineCortical mean diffusivityAmyloid-positive participantsEntorhinal cortexAmyloid statusCognitively normal older adultsHarvard Aging Brain StudyInferior temporal lobeNormal older adultsOlder adultsAging Brain StudyCognitively normal participantsTau accumulationCognitively normal individualsBrain microstructural changesInteraction effectsTau PET imagingDelayed recallBaseline amyloid statusTemporal lobeEntorhinal tauNormal participantsBrain studies
2022
The role of cortical microstructural changes on longitudinal accumulation of tau and cognitive decline in at risk older adults
Gagliardi G, Rodriguez‐Vieitez E, Montal V, Sepulcre J, Diez I, Lois C, Hanseeuw B, Schultz A, Properzi M, Papp K, Marshall G, Fortea J, Johnson K, Sperling R, Vannini P. The role of cortical microstructural changes on longitudinal accumulation of tau and cognitive decline in at risk older adults. Alzheimer's & Dementia 2022, 18 DOI: 10.1002/alz.065744.Peer-Reviewed Original ResearchCortical mean diffusivityCognitive declineOlder adultsCognitively-normal older adultsHarvard Aging Brain StudyAD-related cognitive declinePreclinical Alzheimer Cognitive CompositeCognitively-normal adultsAging Brain StudyAccumulation of tau pathologyAPOE e4 statusBrain microstructural changesCognitive compositeTau accumulationPACC5Gray-matterCognitive AssessmentCognitive impairmentFTP-PETAt-risk individualsAPOE-e4 carriersBrain studiesApo E4E4 statusMean diffusivityNetwork 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 cortexTanglesProteinApoTraitsAlzheimerAlzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy
Brody AH, Nies SH, Guan F, Smith LM, Mukherjee B, Salazar SA, Lee S, Lam TKT, Strittmatter SM. Alzheimer risk gene product Pyk2 suppresses tau phosphorylation and phenotypic effects of tauopathy. Molecular Neurodegeneration 2022, 17: 32. PMID: 35501917, PMCID: PMC9063299, DOI: 10.1186/s13024-022-00526-y.Peer-Reviewed Original ResearchConceptsPS19 miceTau phosphorylationDisease riskPyk2 expressionPyk2 activityHuman neuronal culturesAlzheimer's disease riskNeuro-inflammationSynapse lossTau accumulationTau pathologyMouse survivalC1q depositionT cellsAssociated pathologyMouse modelLittermate controlsMAPK activityHuman neuronsHuman tauNeuronal culturesPyk2 inhibitionVivo modelMouse brainSynaptic function
2021
Spreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-β
Nies SH, Takahashi H, Herber CS, Huttner A, Chase A, Strittmatter SM. Spreading of Alzheimer tau seeds is enhanced by aging and template matching with limited impact of amyloid-β. Journal Of Biological Chemistry 2021, 297: 101159. PMID: 34480901, PMCID: PMC8477193, DOI: 10.1016/j.jbc.2021.101159.Peer-Reviewed Original ResearchConceptsTau seedsAlzheimer's diseaseAD model miceWT mouse brainPathological tauSynaptic lossTau accumulationWT miceMouse tauTau pathologyTau burdenModel miceTau inclusionsPharmacological interventionsAD riskCognitive declineMouse brainTau aggregatesPyk2 kinaseKnowledge of factorsKinase inhibitorsMiceFyn kinase inhibitorAβMouse agingNetwork 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
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