2024
Amyloid-β predominant Alzheimer’s disease neuropathologic change
Kovacs G, Katsumata Y, Wu X, Aung K, Fardo D, Forrest S, Bowen J, Crane P, Jarvik G, Keene C, Larson E, McCormick W, McCurry S, Mukherjee S, Kowall N, McKee A, Stern R, Baldwin C, Farrer L, Jun G, Lunetta K, Honig L, Vonsattel J, Williamson J, Small S, Barral S, Reitz C, Vardarajan B, Mayeux R, Burke J, Hulette C, Welsh-Bohmer K, Gearing M, Lah J, Levey A, Wingo T, Apostolova L, Farlow M, Ghetti B, Saykin A, Spina S, Faber K, Foroud T, Albert M, Lyketsos C, Troncoso J, Frosch M, Green R, Growdon J, Hyman B, Tanzi R, Potter H, Dickson D, Ertekin-Taner N, Graff-Radford N, Parisi J, Petersen R, Boeve B, Allen M, Carrasquillo M, Younkin S, Duara R, Buxbaum J, Goate A, Sano M, Masurkar A, Wisniewski T, Bigio E, Mesulam M, Weintraub S, Vassar R, Kaye J, Quinn J, Woltjer R, Barnes L, Yu L, Evans D, Henderson V, Fallon K, Harrell L, Marson D, Roberson E, DeCarli C, Jin L, Olichney J, Kim R, LaFerla F, Monuki E, Head E, Sultzer D, Geschwind D, Vinters H, Chesselet M, Galasko D, Brewer J, Boxer A, Karydas A, Kramer J, Miller B, Rosen H, Seeley W, Burns J, Swerdlow R, Van Eldik L, Albin R, Lieberman A, Paulson H, Arnold S, Trojanowski J, Van Deerlin V, Cantwell L, Kuzma A, Malamon J, Naj A, Qu L, Schellenberg G, Valladares O, Wang L, Zhao Y, Hamilton R, Kamboh M, Lopez O, Becker J, Cao C, Raj A, Smith A, Chui H, Miller C, Ringman J, Schneider L, Bird T, Sonnen J, Yu C, Grabowsk T, Peskind E, Raskind M, Li G, Tsuang D, Asthana S, Atwood C, Carlsson C, Sager M, Chin N, Craft S, Cairns N, Morris J, Cruchaga C, Strittmatter S, Reiman E, Beach T, Huentelman M, Hardy J, Kauwe J, Hakonarson H, Blacker D, Montine T, Bush W, Haines J, Lerner A, Zhou X, Beecham G, Carney R, Cuccaro M, Gilbert J, Hamilton-Nelson K, Kunkle B, Martin E, Pericak-Vance M, Vance J, Myers A, Leverenz J, De Jager P, Katz M, Lipton R, Pavlik V, Massman P, Darby E, Rodriguear M, Khaleeq A, Royall D, Stevens A, Ory M, DeToledo J, Wilms H, Johnson K, Perez V, Hernandez M, Wilhelmsen K, Tilson J, Chasse S, Barber R, Fairchild T, O’Bryant S, Knebl J, Hall J, Johnson L, Mains D, Alvarez L, Gamboa A, Paydarfar D, Bertelson J, Woon M, Ayres G, Aguirre A, Palmer R, Polk M, Adams P, Huebinger R, Reisch J, Rosenberg R, Cullum M, Williams B, Quiceno M, Hynan L, Smith J, Davis B, Nguyen T, Rogaeva E, George-Hyslop P, Nelson P. Amyloid-β predominant Alzheimer’s disease neuropathologic change. Brain 2024, 148: 401-407. PMID: 39417691, PMCID: PMC11788189, DOI: 10.1093/brain/awae325.Peer-Reviewed Original ResearchTranscriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in a Drosophila knock-in tauopathy model
Bukhari H, Nithianadam V, Battaglia R, Cicalo A, Sarkar S, Comjean A, Hu Y, Leventhal M, Dong X, Feany M. Transcriptional programs mediating neuronal toxicity and altered glial-neuronal signaling in a Drosophila knock-in tauopathy model. Genome Research 2024, 34: gr.278576.123. PMID: 38599684, PMCID: PMC11146598, DOI: 10.1101/gr.278576.123.Peer-Reviewed Original ResearchConceptsGenetic contextNon-cell-autonomous regulationMicrotubule-associated protein tauHuman diseasesGlial-neuronal signalingGene regulatory programsKnock-in fliesTau P301L mutationFrontotemporal dementiaProtein interaction networkModel of tauopathyAge-dependent neurodegenerationSingle-cell RNA sequencingCell signaling pathwaysExperimental model organismAccumulate DNA damageModel of frontotemporal dementiaAutosomal dominant formSingle-cell sequencing analysisPathways of neurotoxicityProtein tauP301L mutationTauopathy modelNeuronal cell typesSequence analysisReduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase
Takahashi H, Bhagwagar S, Nies S, Ye H, Han X, Chiasseu M, Wang G, Mackenzie I, Strittmatter S. Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase. Nature Communications 2024, 15: 1434. PMID: 38365772, PMCID: PMC10873339, DOI: 10.1038/s41467-024-45692-3.Peer-Reviewed Original ResearchConceptsTau inclusionsComorbid proteinopathiesTau aggregation in vitroPromotes tau aggregation in vitroAlzheimer's diseaseProgranulin reductionTDP-43 proteinopathyTauopathy phenotypeTau aggregationAD-tauHuman tauopathiesNeurofibrillary tanglesTauopathy miceReduction of progranulinPurified GlcCerTDP-43Concomitant accumulationAggregation in vitroAssociated with synucleinopathiesNeurodegenerative disordersProteinopathiesGCase inhibitionTauGCaseGlcCerHead-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases
Aguero C, Dhaynaut M, Amaral A, Moon S, Neelamegam R, Scapellato M, Carazo-Casas C, Kumar S, El Fakhri G, Johnson K, Frosch M, Normandin M, Gómez-Isla T. Head-to-head comparison of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 postmortem binding across the spectrum of neurodegenerative diseases. Acta Neuropathologica 2024, 147: 25. PMID: 38280071, PMCID: PMC10822013, DOI: 10.1007/s00401-023-02672-z.Peer-Reviewed Original ResearchConceptsNon-AD tauopathiesTau aggregationTau PET tracersDNA-binding proteinsBinds to neurofibrillary tanglesSecond-generation tau tracersTransactive response DNA-binding proteinSpectrum of neurodegenerative diseasesNeurofibrillary tanglesTau lesionsMelanin-containing cellsTDP-43Binding signalTauopathiesBinding targetsCerebral amyloid angiopathyOff-target bindingB-amyloidBinding patternsNeurodegenerative diseasesTau tracersTauBinding to areasBinding profilesBinding
2023
Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration
Koga S, Metrick M, Golbe L, Santambrogio A, Kim M, Soto-Beasley A, Walton R, Baker M, De Castro C, DeTure M, Russell D, Navia B, Sandiego C, Ross O, Vendruscolo M, Caughey B, Dickson D. Case report of a patient with unclassified tauopathy with molecular and neuropathological features of both progressive supranuclear palsy and corticobasal degeneration. Acta Neuropathologica Communications 2023, 11: 88. PMID: 37264457, PMCID: PMC10236843, DOI: 10.1186/s40478-023-01584-z.Peer-Reviewed Original ResearchConceptsSuperior frontal gyrusFrontal gyrusConsistent with corticobasal degenerationConsistent with progressive supranuclear palsyMotor cortexCorticobasal degenerationProgressive supranuclear palsyPosterior cortical areasPresentation of corticobasal degenerationSubtype of frontotemporal lobar degenerationRichardson's syndromeBrain regionsOccipital cortexSubcortical structuresCaudate nucleusFrontotemporal lobar degenerationTau PET scansSubstantia nigraGlobus pallidusCorticobasal syndromeGyrusSupranuclear palsyCortexCortical areasClinical presentation of progressive supranuclear palsy
2022
Alzheimer 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 functionThe lateral entorhinal cortex is a hub for local and global dysfunction in early Alzheimer’s disease states
Mandino F, Yeow LY, Bi R, Sejin L, Bae HG, Baek SH, Lee CY, Mohammad H, Horien C, Teoh CL, Lee JH, Lai MK, Jung S, Fu Y, Olivo M, Gigg J, Grandjean J. The lateral entorhinal cortex is a hub for local and global dysfunction in early Alzheimer’s disease states. Cerebrovascular And Brain Metabolism Reviews 2022, 42: 1616-1631. PMID: 35466772, PMCID: PMC9441719, DOI: 10.1177/0271678x221082016.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseEntorhinal cortexFunctional connectivity lossEarly AD stagesEarly Alzheimer's diseaseLateral entorhinal cortexVentral networkSynaptic hyperexcitabilityAD progressionGlobal dysfunctionMouse modelOptogenetic activationProjection targetsPathophysiological modelAD stagesMice showNetwork alterationsActive phenotypeNeuronal facilitationEarly hallmarkDiseaseActivity alterationsFMRI signalsNeuronal underpinningsTauopathies
2021
Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET
Song M, Beyer L, Kaiser L, Barthel H, van Eimeren T, Marek K, Nitschmann A, Scheifele M, Palleis C, Respondek G, Kern M, Biechele G, Hammes J, Bischof G, Barbe M, Onur Ö, Jessen F, Saur D, Schroeter M, Rumpf J, Rullmann M, Schildan A, Patt M, Neumaier B, Barret O, Madonia J, Russell D, Stephens A, Mueller A, Roeber S, Herms J, Bötzel K, Danek A, Levin J, Classen J, Höglinger G, Bartenstein P, Villemagne V, Drzezga A, Seibyl J, Sabri O, Boening G, Ziegler S, Brendel M. Binding characteristics of [18F]PI-2620 distinguish the clinically predicted tau isoform in different tauopathies by PET. Cerebrovascular And Brain Metabolism Reviews 2021, 41: 2957-2972. PMID: 34044665, PMCID: PMC8545042, DOI: 10.1177/0271678x211018904.Peer-Reviewed Original ResearchThe 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 ResearchMeSH KeywordsAdultAlzheimer DiseaseAmyloid beta-PeptidesHumansPositron-Emission Tomographytau ProteinsTauopathiesConceptsPositron 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
Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2− production
Chun H, Im H, Kang YJ, Kim Y, Shin JH, Won W, Lim J, Ju Y, Park YM, Kim S, Lee SE, Lee J, Woo J, Hwang Y, Cho H, Jo S, Park JH, Kim D, Kim DY, Seo JS, Gwag BJ, Kim YS, Park KD, Kaang BK, Cho H, Ryu H, Lee CJ. Severe reactive astrocytes precipitate pathological hallmarks of Alzheimer’s disease via H2O2− production. Nature Neuroscience 2020, 23: 1555-1566. PMID: 33199896, DOI: 10.1038/s41593-020-00735-y.Peer-Reviewed Original ResearchConceptsReactive astrocytesAlzheimer's diseaseAPP/PS1 micePathogenesis of ADReactivity of astrocytesBrains of patientsAppropriate experimental modelsGlial activationPS1 miceAstrocytic reactivityBrain atrophyPathological featuresNeuronal deathMonoamine oxidase BPathological hallmarkAD modelPrecise molecular mechanismsAnimal modelsAstrocytesCognitive impairmentPathological contributionExperimental modelDiseaseOxidase BEventual deathHypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease
Arnsten AFT, Datta D, Del Tredici K, Braak H. Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer's disease. Alzheimer's & Dementia 2020, 17: 115-124. PMID: 33075193, PMCID: PMC7983919, DOI: 10.1002/alz.12192.Peer-Reviewed Original ResearchConceptsAbnormal tau phosphorylationTau pathologyProjection neuronsTau phosphorylationAssociation cortexAlzheimer's diseaseBrain tau pathologySporadic Alzheimer's diseaseSusceptible microenvironmentCalcium dysregulationVulnerable neuronsAβ plaquesAβ productionSporadic formsSAD pathologyRhesus monkeysAbnormal phosphorylationPathological eventsDiseaseAβ oligomersPathologyNeuronsVicious cycleCortexTauFyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy
Tang SJ, Fesharaki-Zadeh A, Takahashi H, Nies SH, Smith LM, Luo A, Chyung A, Chiasseu M, Strittmatter SM. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathologica Communications 2020, 8: 96. PMID: 32611392, PMCID: PMC7329553, DOI: 10.1186/s40478-020-00976-9.Peer-Reviewed Original ResearchConceptsRepetitive closed head injuriesMemory deficitsPhospho-tau accumulationChronic variable stressPersistent memory deficitsP301S transgenic miceClosed head injuryFyn inhibitionPassive avoidance learningFyn kinaseGlial activationPhospho-tauPresynaptic markersSynapse lossTau accumulationHead injurySynapse densityPhosphorylated tauTherapeutic benefitTransgenic miceBehavioral improvementTrauma modelTauopathiesSpatial memoryAvoidance learning
2019
Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults
Vannini P, Uquillas F, Jacobs H, Sepulcre J, Gatchel J, Amariglio R, Hanseeuw B, Papp K, Hedden T, Rentz D, Pascual-Leone A, Johnson K, Sperling R. Decreased meta-memory is associated with early tauopathy in cognitively unimpaired older adults. NeuroImage Clinical 2019, 24: 102097. PMID: 31795044, PMCID: PMC6879982, DOI: 10.1016/j.nicl.2019.102097.Peer-Reviewed Original ResearchConceptsFeeling-of-knowingEpisodic feeling-of-knowingCognitively unimpaired older adultsMeta-memoryMedial temporal lobe regionsOlder adultsFace-name pairsRegion-of-interest analysisTemporal lobe regionsAlzheimer's diseaseVoxel-wise correlationSemantic knowledge networkTemporal poleLobe regionsEntorhinal cortexNon-famousSensitive clinical indicatorMulti-tracer PETMemory efficiencySemantic informationAdultsTau pathologyAD pathophysiologyParticipantsPET data[18F]-AV-1451 binding profile in chronic traumatic encephalopathy: a postmortem case series
Marquié M, Agüero C, Amaral A, Villarejo-Galende A, Ramanan P, Chong M, Sáez-Calveras N, Bennett R, Verwer E, Kim S, Dhaynaut M, Alvarez V, Johnson K, McKee A, Frosch M, Gómez-Isla T. [18F]-AV-1451 binding profile in chronic traumatic encephalopathy: a postmortem case series. Acta Neuropathologica Communications 2019, 7: 164. PMID: 31661038, PMCID: PMC6816221, DOI: 10.1186/s40478-019-0808-1.Peer-Reviewed Original ResearchConceptsTau aggregationPositron emission tomographyTau lesionsPresence of tau aggregatesInferior parietal cortexSuperior temporal cortexPaired helical filamentsTau seeding activityHyperphosphorylated tau speciesDetection of tau aggregatesTraumatic encephalopathyPostmortem brain tissue samplesCorticobasal degenerationProgressive supranuclear palsyBinding profilesTau-containing lesionsRepetitive head traumaDifferential binding affinityFrontal cortexTemporal cortexParietal cortexTau conformationTau speciesBinding affinityOccipital cortex
2017
Pathological correlations of [F‐18]‐AV‐1451 imaging in non‐alzheimer tauopathies
Marquié M, Normandin M, Meltzer A, Chong M, Andrea N, Antón‐Fernández A, Klunk W, Mathis C, Ikonomovic M, Debnath M, Bien E, Vanderburg C, Costantino I, Makaretz S, DeVos S, Oakley D, Gomperts S, Growdon J, Domoto‐Reilly K, Lucente D, Dickerson B, Frosch M, Hyman B, Johnson K, Gómez‐Isla T. Pathological correlations of [F‐18]‐AV‐1451 imaging in non‐alzheimer tauopathies. Annals Of Neurology 2017, 81: 117-128. PMID: 27997036, PMCID: PMC5319193, DOI: 10.1002/ana.24844.Peer-Reviewed Original ResearchConceptsNon-Alzheimer tauopathiesTau lesionsDetection of tau aggregatesBinding to tau lesionsTau measuresPositron emission tomographyMutation carriersTau filamentsProgressive supranuclear palsyTau aggregationPostmortem brain samplesAlzheimer brainsTauopathiesAV-1451Atypical tauopathyBrain regionsOff-target bindingBinding patternsBinding assaysBasal gangliaEntorhinal cortexSubstantia nigraTauMAPT
2015
Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue
Marquié M, Normandin M, Vanderburg C, Costantino I, Bien E, Rycyna L, Klunk W, Mathis C, Ikonomovic M, Debnath M, Vasdev N, Dickerson B, Gomperts S, Growdon J, Johnson K, Frosch M, Hyman B, Gómez-Isla T. Validating novel tau positron emission tomography tracer [F‐18]‐AV‐1451 (T807) on postmortem brain tissue. Annals Of Neurology 2015, 78: 787-800. PMID: 26344059, PMCID: PMC4900162, DOI: 10.1002/ana.24517.Peer-Reviewed Original ResearchConceptsTau filamentsAlzheimer brainsTDP-43Paired helical filamentsDNA-binding proteinsIn vitro binding assaysFrontotemporal lobar degeneration-tauBinding to tau lesionsDNA-binding protein 43Tauopathy brainsHelical filamentsBrain tau pathologyTau pathologyTau lesionsSubstrate-specificBinding proteinPostmortem brain tissueCerebral amyloid angiopathyPhosphor-screen autoradiographyOff-target bindingB-amyloidAlzheimer's diseaseBinding assaysTauProtein 43
2009
Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head Injury
McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. Chronic Traumatic Encephalopathy in Athletes: Progressive Tauopathy After Repetitive Head Injury. Journal Of Neuropathology & Experimental Neurology 2009, 68: 709-735. PMID: 19535999, PMCID: PMC2945234, DOI: 10.1097/nen.0b013e3181a9d503.Peer-Reviewed Original ResearchConceptsChronic traumatic encephalopathyTraumatic encephalopathyProgressive tauopathyTau-immunoreactive neurofibrillary tanglesRepetitive brain traumaRepetitive head injuryProgressive neurological deteriorationCavum septum pellucidumSuperficial cortical layersMedial temporal lobeAstrocytic tanglesTau-immunoreactiveNeurological deteriorationDementia pugilisticaVentricular dilatationBrain traumaHead injurySeptum pellucidumNeurofibrillary degenerationMammillary bodiesNeurofibrillary tanglesDiffuse plaquesGait abnormalitiesMemory disturbanceTemporal lobe
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