2023
Prion Protein Complex with mGluR5 Mediates Amyloid-ß Synaptic Loss in Alzheimer’s Disease
Roseman G, Fu L, Strittmatter S. Prion Protein Complex with mGluR5 Mediates Amyloid-ß Synaptic Loss in Alzheimer’s Disease. 2023, 467-481. DOI: 10.1007/978-3-031-20565-1_22.ChaptersAlzheimer's diseaseMouse modelAD transgenic mouse modelLong-term potentiation impairmentPrimary histopathological featureAD mouse modelAmyloid-beta plaquesTransgenic mouse modelPotential therapeutic targetSynaptic lossHistopathological featuresAD pathophysiologyNeuronal dysfunctionSynapse densityCognitive dysfunctionNeurofibrillary tanglesTherapeutic targetMemory deficitsCellular prion proteinMGluR5DiseaseCell death characteristicCommon formSynaptotoxicityDysfunction
2022
Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q
Spurrier J, Nicholson L, Fang XT, Stoner AJ, Toyonaga T, Holden D, Siegert TR, Laird W, Allnutt MA, Chiasseu M, Brody AH, Takahashi H, Nies SH, Pérez-Cañamás A, Sadasivam P, Lee S, Li S, Zhang L, Huang YH, Carson RE, Cai Z, Strittmatter SM. Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science Translational Medicine 2022, 14: eabi8593. PMID: 35648810, PMCID: PMC9554345, DOI: 10.1126/scitranslmed.abi8593.Peer-Reviewed Original ResearchConceptsPositron emission tomographySilent allosteric modulatorsAlzheimer's diseaseMouse modelPhospho-tau accumulationAged mouse modelAlzheimer mouse modelImmune-mediated attackSAM treatmentMicroglial mediatorsSynaptic engulfmentSynaptic lossAD miceComplement component C1qSynapse lossGlutamate responseSynaptic densityDrug washoutSynaptic localizationTherapeutic benefitCognitive impairmentAllosteric modulatorsEmission tomographyNonhuman primatesComponent C1q
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 aging
2016
Early Activation of Experience-Independent Dendritic Spine Turnover in a Mouse Model of Alzheimer's Disease.
Heiss JK, Barrett J, Yu Z, Haas LT, Kostylev MA, Strittmatter SM. Early Activation of Experience-Independent Dendritic Spine Turnover in a Mouse Model of Alzheimer's Disease. Cerebral Cortex 2016, 27: 3660-3674. PMID: 27365298, PMCID: PMC6059166, DOI: 10.1093/cercor/bhw188.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAlzheimer DiseaseAmyloid beta-Protein PrecursorAnalysis of VarianceAnimalsCerebral CortexDendritic SpinesDisease Models, AnimalGene Expression ProfilingGreen Fluorescent ProteinsHippocampusHumansImaging, Three-DimensionalImmunoprecipitationMiceMice, Inbred C57BLMice, TransgenicMutationNeuroimagingPlaque, AmyloidPresenilin-1Prion ProteinsProto-Oncogene Proteins c-fosSensory DeprivationTime FactorsVibrissaeConceptsAPP/PS1 miceDendritic spine turnoverSpine turnoverAlzheimer's diseasePS1 miceAged APP/PS1 miceYoung APP/PS1 miceAPP/PS1 mouse brainSoluble Aβ oligomersLipid-metabolizing genesAPPswe/Synaptic lossCerebral cortexSynapse densityAβ plaquesSynaptic dysregulationLack responsivenessMouse modelDendritic spinesPersistent spinesSynapse turnoverPlaque formationMouse brainYounger ageCellular prion protein