2024
Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease
Xicota L, Cosentino S, Vardarajan B, Mayeux R, Perls T, Andersen S, Zmuda J, Thyagarajan B, Yashin A, Wojczynski M, Krinsky‐McHale S, Handen B, Christian B, Head E, Mapstone M, Schupf N, Lee J, Barral S, Study T, Abner E, Adams P, Aguirre A, Albert M, Albin R, Allen M, Alvarez L, Andrews H, Apostolova L, Arnold S, Asthana S, Atwood C, Ayres G, Barber R, Barnes L, Barral S, Bartlett J, Beach T, Becker J, Beecham G, Benchek P, Bennett D, Bertelson J, Biber S, Bird T, Blacker D, Boeve B, Bowen J, Boxer A, Brewer J, Burke J, Burns J, Bush W, Buxbaum J, Byrd G, Cantwell L, Cao C, Carlsson C, Carrasquillo M, Chan K, Chasse S, Chen Y, Chesselet M, Chin N, Chui H, Chung J, Craft S, Crane P, Cranney M, Cruchaga C, Cuccaro M, Culhane J, Cullum C, Darby E, Davis B, De Jager P, DeCarli C, DeToledo J, Dickson D, Dobbins N, Duara R, Ertekin‐Taner N, Evans D, Faber K, Fairchild T, Fallin D, Fallon K, Fardo D, Farlow M, Farrell J, Farrer L, Fernandez‐Hernandez V, Foroud T, Frosch M, Galasko D, Gamboa A, Gauthreaux K, Gefen T, Geschwind D, Ghetti B, Gilbert J, Goate A, Grabowski T, Graff‐Radford N, Griswold A, Haines J, Hakonarson H, Hall K, Hall J, Hamilton R, Hamilton‐Nelson K, Han X, Harari O, Hardy J, Harrell L, Head E, Henderson V, Hernandez M, Honig L, Huebinger R, Huentelman M, Hulette C, Hyman B, Hynan L, Ibanez L, Jarvik G, Jayadev S, Jin L, Johnson K, Johnson L, Jones B, Jun G, Kamboh M, Kang M, Karydas A, Katz M, Kauwe J, Kaye J, Keene C, Keller B, Khaleeq A, Kim R, Knebl J, Kowall N, Kramer J, Kukull W, Kunkle B, Kuzma A, LaFerla F, Lah J, Larson E, Lerch M, Lerner A, Leung Y, Leverenz J, Levey A, Lieberman A, Lipton R, Lopez O, Lunetta K, Lyketsos C, Mains D, Manly J, Mark L, Marquez D, Marson D, Martin E, Masliah E, Massman P, Masurkar A, Mayeux R, McCormick W, McCurry S, McDonough S, McKee A, Mesulam M, Mez J, Miller B, Miller C, Mock C, Moghekar A, Montine T, Monuki E, Mooney S, Morris J, Mukherjee S, Myers A, Naj A, Nguyen T, Noble J, Nudelman K, O'Bryant S, Ormsby K, Ory M, Palmer R, Parisi J, Paulson H, Pavlik V, Paydarfar D, Perez V, Pericak‐Vance M, Petersen R, Polk M, Qu L, Quiceno M, Quinn J, Raj A, Rajabli F, Ramanan V, Reiman E, Reisch J, Reitz C, Ringman J, Roberson E, Rodriguear M, Rogaeva E, Rosen H, Rosenberg R, Royall D, Sano M, Saykin A, Schellenberg G, Schneider J, Schneider L, Seeley W, Sherva R, Shibata D, Small S, Smith A, Smith J, Song Y, Spina S, St George‐Hyslop P, Stern R, Stevens A, Strittmatter S, Sultzer D, Swerdlow R, Teich A, Tilson J, Tosto G, Trojanowski J, Troncoso J, Tsuang D, Valladares O, Van Deerlin V, Van Dyck C, Van Eldik L, Vance J, Vardarajan B, Vassar R, Vinters H, Wang L, Weintraub S, Welsh‐Bohmer K, Wheeler N, Wijsman E, Wilhelmsen K, Williams B, Williamson J, Wilms H, Wingo T, Wisniewski T, Woltjer R, Woon M, Younkin S, Yu L, Zhao Y, Zhou X, Zhu C, Aizenstein H, Ances B, Andrews H, Bell K, Birn R, Brickman A, Bulova P, Cheema A, Chen K, Christian B, Clare I, Cohen A, Constantino J, Doran E, Fagan A, Feingold E, Foroud T, Handen B, Harp J, Hartley S, Head E, Henson R, Hom C, Honig L, Ikonomovic M, Johnson S, Jordan C, Kamboh M, Keator D, Klunk W, Kofler J, Krinsky‐McHale S, Lai F, Lao P, Laymon C, Lee J, Lott I, Lupson V, Mapstone M, Mathis C, Minhas D, Nadkarni N, O'Bryant S, Parisi M, Pang D, Petersen M, Price J, Pulsifer M, Rafii M, Reiman E, Rizvi B, Rosas H, Ryan L, Schmitt F, Schupf N, Silverman W, Tudorascu D, Tumuluru R, Varadarajan B, White D, Yassa M, Zaman S, Zhang F. Whole genome‐wide sequence analysis of long‐lived families (Long‐Life Family Study) identifies MTUS2 gene associated with late‐onset Alzheimer's disease. Alzheimer's & Dementia 2024, 20: 2670-2679. PMID: 38380866, PMCID: PMC11032545, DOI: 10.1002/alz.13718.Peer-Reviewed Original ResearchConceptsLate-onset Alzheimer's diseaseGenes associated with late-onset Alzheimer's diseaseLate-onset Alzheimer's disease riskSeveral single nucleotide polymorphismsVariants associated with late-onset Alzheimer diseaseBeta-amyloidIdentified several single nucleotide polymorphismsWhole-genome sequence analysisGenome sequence analysisLevels of beta-amyloidAlzheimer's diseaseTight linkage disequilibriumMicrotubule associated proteinSingle nucleotide polymorphismsFamily studiesCandidate lociMTUS2Linkage disequilibriumSequence analysisAssociation analysisNucleotide polymorphismsGenetic associationAlzheimer's dementiaAssociated proteinGenetic component
2023
Neuronal 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 ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsDisease Models, AnimalMiceMice, TransgenicNeuronsPrion ProteinsPrionsSynapsesTau ProteinsTranscriptomeConceptsSynapse 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 age
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 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 ResearchMeSH KeywordsAgingAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCerebral CortexHippocampusMiceMice, KnockoutNeuritesTau ProteinsConceptsTau 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 aging
2019
Anti‐PrPC antibody rescues cognition and synapses in transgenic alzheimer mice
Cox TO, Gunther EC, Brody AH, Chiasseu MT, Stoner A, Smith LM, Haas LT, Hammersley J, Rees G, Dosanjh B, Groves M, Gardener M, Dobson C, Vaughan T, Chessell I, Billinton A, Strittmatter SM. Anti‐PrPC antibody rescues cognition and synapses in transgenic alzheimer mice. Annals Of Clinical And Translational Neurology 2019, 6: 554-574. PMID: 30911579, PMCID: PMC6414488, DOI: 10.1002/acn3.730.Peer-Reviewed Original ResearchConceptsAPP/PS1 transgenic micePS1 transgenic miceBrain antibodiesTransgenic miceDisease pathophysiologyDisease pathologyTransgenic Alzheimer's miceAlzheimer's disease pathologyAlzheimer's disease pathophysiologyHuman monoclonal antibodyPreclinical therapeutic efficacyHigh-affinity receptorAmyloid-beta oligomersLast doseTransgenic brainsPlaque pathologyAlzheimer's micePreclinical dataSynaptic damageAnti-PrPc antibodiesSynaptic densityIntraperitoneal dosingBrain biochemistryCentral synapsesTherapeutic efficacySystematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance
Smith LM, Kostylev MA, Lee S, Strittmatter SM. Systematic and standardized comparison of reported amyloid-β receptors for sufficiency, affinity, and Alzheimer's disease relevance. Journal Of Biological Chemistry 2019, 294: 6042-6053. PMID: 30787106, PMCID: PMC6463724, DOI: 10.1074/jbc.ra118.006252.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAD brainLeukocyte immunoglobulin-like receptorsNogo receptor 1Human AD brainsImmunoglobulin-like receptorsB member 2Brains of individualsReceptor candidatesSoluble AβOsDisease relevanceCell surface expressionHippocampal neuronsMouse modelSynthetic AβAβO bindingMemory impairmentReceptor 1Cellular prion proteinNeuronal synapsesNgR1Molecular pathologyAβAβ speciesMember 2Pyk2 Signaling through Graf1 and RhoA GTPase Is Required for Amyloid-β Oligomer-Triggered Synapse Loss
Lee S, Salazar SV, Cox TO, Strittmatter SM. Pyk2 Signaling through Graf1 and RhoA GTPase Is Required for Amyloid-β Oligomer-Triggered Synapse Loss. Journal Of Neuroscience 2019, 39: 1910-1929. PMID: 30626696, PMCID: PMC6407289, DOI: 10.1523/jneurosci.2983-18.2018.Peer-Reviewed Original ResearchConceptsDendritic spine lossGenetic variationRhoA GTPaseSynapse lossSpine lossBiochemical basisGTPase-activating proteinsFocal adhesion kinasePyk2 functionPyk2 tyrosine kinasePostsynaptic sitesTyrosine kinase Pyk2Disease riskKinase-dependent mechanismOverexpression of Pyk2Dendritic spine densityAdhesion kinaseTransgenic mouse modelBiochemical isolationPyk2 kinaseAlzheimer's disease riskDendritic spine stabilityKinase Pyk2Late-onset Alzheimer's disease (LOAD) riskActin control
2018
Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β-Induced Synaptic Dysfunction and Loss
Salazar SV, Cox TO, Lee S, Brody AH, Chyung AS, Haas LT, Strittmatter SM. Alzheimer's Disease Risk Factor Pyk2 Mediates Amyloid-β-Induced Synaptic Dysfunction and Loss. Journal Of Neuroscience 2018, 39: 758-772. PMID: 30518596, PMCID: PMC6343652, DOI: 10.1523/jneurosci.1873-18.2018.Peer-Reviewed Original ResearchConceptsTransgenic AD model miceAD model miceAbsence of Pyk2Synaptic dysfunctionModel miceHippocampal slicesSynaptic transmissionAlzheimer's diseaseAmyloid-β plaque pathologyHippocampal Schaffer collateral pathwayDisease riskLearning/memory deficitsDeletion of Pyk2Suppression of LTPBasal synaptic transmissionLate-onset Alzheimer's diseaseImpairment of learningSchaffer collateral pathwayAD-related synaptic dysfunctionAlzheimer's disease riskLate-onset Alzheimer's disease (LOAD) riskOnset Alzheimer's diseaseAge-dependent lossMechanism of actionSynaptic LTDLiquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer’s Amyloid-β Oligomers
Kostylev MA, Tuttle MD, Lee S, Klein LE, Takahashi H, Cox TO, Gunther EC, Zilm KW, Strittmatter SM. Liquid and Hydrogel Phases of PrPC Linked to Conformation Shifts and Triggered by Alzheimer’s Amyloid-β Oligomers. Molecular Cell 2018, 72: 426-443.e12. PMID: 30401430, PMCID: PMC6226277, DOI: 10.1016/j.molcel.2018.10.009.Peer-Reviewed Original ResearchConceptsAmino-terminal GlyCellular prion proteinProtein phase separationAmyloid-β OligomersPlasma membraneMembraneless organellesAla residuesRecombinant PrPPrion proteinCell surfaceConformation shiftConformational transitionHelical conformationAβ speciesPrPSupSpongiform degenerationEndogenous AβOsOrganellesPrPCSuch domainsSpeciesDomainProteinAβOsSleep and EEG Power Spectral Analysis in Three Transgenic Mouse Models of Alzheimer’s Disease: APP/PS1, 3xTgAD, and Tg2576
Kent BA, Strittmatter SM, Nygaard H. Sleep and EEG Power Spectral Analysis in Three Transgenic Mouse Models of Alzheimer’s Disease: APP/PS1, 3xTgAD, and Tg2576. Journal Of Alzheimer's Disease 2018, 64: 1325-1336. PMID: 29991134, PMCID: PMC6176720, DOI: 10.3233/jad-180260.Peer-Reviewed Original Research
2017
Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer's model
Smith LM, Zhu R, Strittmatter SM. Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer's model. Neuropharmacology 2017, 130: 54-61. PMID: 29191754, PMCID: PMC5743608, DOI: 10.1016/j.neuropharm.2017.11.042.Peer-Reviewed Original ResearchConceptsAlzheimer's modelDisease-modifying effectsDisease-modifying therapiesMouse Alzheimer’s modelsTherapy withdrawalAPPswe/Investigational agentsSynapse densityDrug washoutTransgenic modelAlzheimer's diseasePersistent benefitsPersistent improvementSaracatinibFyn inhibitorMemantineLoss of benefitDiseaseSpatial memoryMemory functionWashoutTherapySymptomsMiceWeeksChapter Thirteen Synaptotoxic Signaling by Amyloid Beta Oligomers in Alzheimer's Disease Through Prion Protein and mGluR5
Brody AH, Strittmatter SM. Chapter Thirteen Synaptotoxic Signaling by Amyloid Beta Oligomers in Alzheimer's Disease Through Prion Protein and mGluR5. Advances In Pharmacology 2017, 82: 293-323. PMID: 29413525, PMCID: PMC5835229, DOI: 10.1016/bs.apha.2017.09.007.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsHumansPrion ProteinsReceptor, Metabotropic Glutamate 5Signal TransductionSynapsesConceptsAlzheimer's diseaseNovel potential therapeutic targetDisease-modifying AD therapiesPotential therapeutic targetAmyloid-beta oligomersPrion proteinSynapse lossTau pathologySynaptic dysfunctionAD symptomsSynaptic damageAD pathophysiologyNeuronal dysfunctionSynaptic toxicityDisease progressionAD progressionAD therapyMemory dysfunctionTherapeutic targetCellular prion proteinBeta oligomersDysfunctionDiseaseGlobal health crisisMGluR5
2016
Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity
Smith LM, Strittmatter SM. Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity. Cold Spring Harbor Perspectives In Medicine 2016, 7: a024075. PMID: 27940601, PMCID: PMC5411685, DOI: 10.1101/cshperspect.a024075.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBinding SitesHumansPlaque, AmyloidPrion ProteinsProtein BindingReceptor, InsulinSignal TransductionConceptsAlzheimer's diseaseAβ oligomersSoluble Aβ oligomersFibrillary amyloidNeuronal impairmentSynaptic dysfunctionAD pathogenesisSynaptic toxicityAmyloid-β OligomersCellular prion proteinNeuronal cascadesFurther studiesCell surface proteinsDiseaseAβPrion proteinOligomer toxicityToxicityDysfunctionMolecular basisPathogenesisDementiaProteinPlaquesImpairmentCellular prion protein as a receptor for amyloid-β oligomers in Alzheimer's disease
Salazar SV, Strittmatter SM. Cellular prion protein as a receptor for amyloid-β oligomers in Alzheimer's disease. Biochemical And Biophysical Research Communications 2016, 483: 1143-1147. PMID: 27639648, PMCID: PMC5303667, DOI: 10.1016/j.bbrc.2016.09.062.Peer-Reviewed Original ResearchConceptsCellular prion proteinPrion proteinSignal transduction downstreamDisease pathophysiologyNeuronal surfaceMetabotropic glutamate receptor 5Neuronal cell surface moleculesGlutamate receptor 5Disease-associated stateAlzheimer's disease pathophysiologyAltered signal transductionTransduction downstreamSignal transductionGenetic evidenceSpecificity of bindingPyk2 kinaseCell surface moleculesFyn kinaseSynaptic dysfunctionAβO toxicitySynaptic transmissionMouse modelIntervention sitesReceptor 5Alzheimer's diseaseOligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease*
Haas LT, Strittmatter SM. Oligomers of Amyloid β Prevent Physiological Activation of the Cellular Prion Protein-Metabotropic Glutamate Receptor 5 Complex by Glutamate in Alzheimer Disease*. Journal Of Biological Chemistry 2016, 291: 17112-17121. PMID: 27325698, PMCID: PMC5016115, DOI: 10.1074/jbc.m116.720664.Peer-Reviewed Original ResearchConceptsProtein tyrosine kinase 2Calmodulin-dependent protein kinase IICalcium/calmodulin-dependent protein kinase IICellular prion proteinProtein kinase IIBrain slicesSignaling cascadesAlzheimer's diseaseKinase IIPhysiological signalingKinase 2Mutant transgeneMetabotropic glutamate receptor 5Loss of synapsesPrion proteinGlutamate receptor 5Receptor complexWild-type slicesProtein mediatorsAmyloid-β OligomersGlutamate activationChronic expressionDementia symptomsReceptor 5Acute exposure
2015
Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models*
Kostylev MA, Kaufman AC, Nygaard HB, Patel P, Haas LT, Gunther EC, Vortmeyer A, Strittmatter SM. Prion-Protein-interacting Amyloid-β Oligomers of High Molecular Weight Are Tightly Correlated with Memory Impairment in Multiple Alzheimer Mouse Models*. Journal Of Biological Chemistry 2015, 290: 17415-17438. PMID: 26018073, PMCID: PMC4498078, DOI: 10.1074/jbc.m115.643577.Peer-Reviewed Original ResearchAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBehavior, AnimalDisease Models, AnimalFemaleHumansMaleMemory DisordersMiceMice, Inbred C57BLMice, Mutant StrainsMice, TransgenicMiddle AgedMolecular WeightPrefrontal CortexPresenilin-1PrionsProtein Structure, QuaternaryPrPC ProteinsRecombinant ProteinsFyn inhibition rescues established memory and synapse loss in Alzheimer mice
Kaufman AC, Salazar SV, Haas LT, Yang J, Kostylev MA, Jeng AT, Robinson SA, Gunther EC, van Dyck CH, Nygaard HB, Strittmatter SM. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Annals Of Neurology 2015, 77: 953-971. PMID: 25707991, PMCID: PMC4447598, DOI: 10.1002/ana.24394.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseTransgenic miceGlu receptorsAPP/PS1 transgenic miceAPP/PS1 miceMemory deficitsEffective disease-modifying agentsAD mouse modelPS1 transgenic miceAD transgenic miceDisease-modifying agentsTau transgenic miceWeeks of treatmentPrecursor protein metabolismSpatial memory deficitsNovel object recognitionMorris water mazeBrain slice assaysAZD0530 treatmentMicroglial activationPS1 miceVehicle treatmentSynapse lossAlzheimer's miceAD pathology
2014
Therapeutic Molecules and Endogenous Ligands Regulate the Interaction between Brain Cellular Prion Protein (PrPC) and Metabotropic Glutamate Receptor 5 (mGluR5)*
Haas LT, Kostylev MA, Strittmatter SM. Therapeutic Molecules and Endogenous Ligands Regulate the Interaction between Brain Cellular Prion Protein (PrPC) and Metabotropic Glutamate Receptor 5 (mGluR5)*. Journal Of Biological Chemistry 2014, 289: 28460-28477. PMID: 25148681, PMCID: PMC4192497, DOI: 10.1074/jbc.m114.584342.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsAntibodiesBinding SitesBiological AssayBrain ChemistryCell MembraneDisease Models, AnimalGene Expression RegulationHEK293 CellsHumansLigandsMiceMice, TransgenicPeptide MappingProtein BindingProtein Structure, TertiaryPrPC ProteinsReceptor, Metabotropic Glutamate 5Recombinant ProteinsSignal TransductionSmall Molecule LibrariesConceptsMetabotropic glutamate receptor 5Glutamate receptor 5Receptor 5Endogenous ligandMouse brainAD transgenic model miceCellular prion proteinAmino acids 91Transgenic model miceSoluble amyloid β (Aβ) oligomersAlzheimer's disease pathophysiologySilent allosteric modulatorsAgonists/antagonistsExtracellular AβOsMGluR5 activitySynthetic AβOsPrion proteinAmyloid-β OligomersModel miceCell membrane preparationsMGluR5Neurotoxic signalsBrain homogenatesAlzheimer's diseaseDisease pathophysiology
2013
Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein
Um JW, Kaufman AC, Kostylev M, Heiss JK, Stagi M, Takahashi H, Kerrisk ME, Vortmeyer A, Wisniewski T, Koleske AJ, Gunther EC, Nygaard HB, Strittmatter SM. Metabotropic Glutamate Receptor 5 Is a Coreceptor for Alzheimer Aβ Oligomer Bound to Cellular Prion Protein. Neuron 2013, 79: 887-902. PMID: 24012003, PMCID: PMC3768018, DOI: 10.1016/j.neuron.2013.06.036.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCalciumCells, CulturedElongation Factor 2 KinaseHEK293 CellsHumansMiceNeuronsOocytesPhosphorylationPost-Synaptic DensityProto-Oncogene Proteins c-fynPrPC ProteinsReceptor, Metabotropic Glutamate 5Receptors, Metabotropic GlutamateSignal TransductionXenopusConceptsDisease pathophysiologyHuman AD brain extractsCellular prion proteinMetabotropic glutamate receptor 5Postsynaptic densityDendritic spine lossAD brain extractsMetabotropic glutamate receptorsGlutamate receptor 5Alzheimer's disease pathophysiologyExtracellular AβOsMGluR5 antagonismPrion proteinSpine lossSynapse densityGlutamate receptorsIntracellular calciumMGluR5Receptor 5Neuronal functionAβOsBrain extractsAβ oligomersFyn kinasePSD proteinsAmyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease
Um JW, Strittmatter SM. Amyloid-β induced signaling by cellular prion protein and Fyn kinase in Alzheimer disease. Prion 2013, 7: 37-41. PMID: 22987042, PMCID: PMC3609048, DOI: 10.4161/pri.22212.Peer-Reviewed Original ResearchConceptsCellular prion proteinPrion proteinSignal transduction downstreamTransduction downstreamAlzheimer's diseaseFyn kinaseFunctional consequencesAβ oligomersAmyloid-β OligomersNeuronal surfaceHigh-affinity receptorOligomer complexesAD-related phenotypesCentral roleProteinAD pathogenesisRecent evidencePrevalent causeTherapeutic interventionsFynKinaseOligomersPhenotypeDiseaseDownstream