2024
Characterizing the Effects of Progranulin Reduction on Tau Pathology and Phenotypes in a Mouse Model of Tauopathy (P4-9.016)
Bhagwagar S, Takahashi H, Strittmatter S. Characterizing the Effects of Progranulin Reduction on Tau Pathology and Phenotypes in a Mouse Model of Tauopathy (P4-9.016). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205227.Peer-Reviewed Original Research
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 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 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 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
2020
Elucidating the role of the AD risk factor Pyk2 in tau‐induced neuronal dysfunction
Brody A, Strittmatter S. Elucidating the role of the AD risk factor Pyk2 in tau‐induced neuronal dysfunction. Alzheimer's & Dementia 2020, 16 DOI: 10.1002/alz.036625.Peer-Reviewed Original ResearchSpatial memory impairmentCell layer thicknessGenetic deletionTau pathologyTau phosphorylationMemory impairmentPharmacological inhibitionAcute hippocampal slice preparationsTau-induced neuronal dysfunctionHippocampal slice preparationPS19 miceNeuronal dysfunctionSlice preparationHistological assessmentMouse modelKnockout micePyk2 activityExacerbationMicePyk2PathologyImpairmentAnimalsTauPhenotype
2017
Chapter 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 ResearchConceptsAlzheimer'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 crisisMGluR5Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network
Takahashi H, Klein ZA, Bhagat SM, Kaufman AC, Kostylev MA, Ikezu T, Strittmatter SM, For the Alzheimer’s Disease Neuroimaging Initiative. Opposing effects of progranulin deficiency on amyloid and tau pathologies via microglial TYROBP network. Acta Neuropathologica 2017, 133: 785-807. PMID: 28070672, PMCID: PMC5391267, DOI: 10.1007/s00401-017-1668-z.Peer-Reviewed Original ResearchConceptsAPP/PS1 micePS1 micePGRN deficiencyAlzheimer's diseaseAD risk variantsCerebrospinal fluid Aβ levelsLoss of progranulinMicroglial Aβ phagocytosisCSF tau levelsFrontotemporal lobar degenerationRisk variantsAPPswe/Aβ phagocytosisNeuronal injuryAβ levelsAβ pathologyCerebral amyloidosisAxonal dystrophyTau pathologyTau levelsComplement depositionPGRN levelsAD pathophysiologyAmyloid imagingProgranulin deficiency