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
2017
Bidirectional regulation of Aβ levels by Presenilin 1
Bustos V, Pulina MV, Kelahmetoglu Y, Sinha SC, Gorelick FS, Flajolet M, Greengard P. Bidirectional regulation of Aβ levels by Presenilin 1. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: 7142-7147. PMID: 28533411, PMCID: PMC5502639, DOI: 10.1073/pnas.1705235114.Peer-Reviewed Original ResearchConceptsAmyloid precursor proteinAβ levelsΓ-secretase complexAlzheimer's diseasePresenilin 1Pathogenesis of ADAβ peptidesEndogenous kinaseΒ-amyloid peptidePS1 functionIntramembranous proteinsCatalytic subunitΓ-secretase activityPlaque loadC-terminal fragmentAutophagic degradationPotential therapySer367Selective phosphorylationSequential proteolysisTransgenic micePhosphorylationCultured cellsΒ-secretaseDiseaseOpposing 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
2014
Effects of corticotrophin-releasing factor receptor 1 antagonists on amyloid-β and behavior in Tg2576 mice
Dong H, Wang S, Zeng Z, Li F, Montalvo-Ortiz J, Tucker C, Akhtar S, Shi J, Meltzer HY, Rice KC, Csernansky JG. Effects of corticotrophin-releasing factor receptor 1 antagonists on amyloid-β and behavior in Tg2576 mice. Psychopharmacology 2014, 231: 4711-4722. PMID: 24862368, PMCID: PMC4233002, DOI: 10.1007/s00213-014-3629-8.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsCorticotropin-Releasing HormoneCyclic AMPCyclic AMP-Dependent Protein KinasesDisease Models, AnimalHippocampusMaleMemoryMiceMice, TransgenicNeuronsPlaque, AmyloidPyrimidinesPyrrolesReceptors, Corticotropin-Releasing HormoneSignal TransductionConceptsAβ1-42 levelsCorticotrophin-releasing factorReceptor 1 antagonistPlaque depositionCRF1 antagonistsMouse modelDays of ageAlzheimer's diseaseMouse pupsIsolation stressCRF receptor 1 antagonistFactor receptor 1 antagonistAdministration of antalarminExogenous CRF administrationCultured primary hippocampal neuronsDaily intraperitoneal injectionsIncubation of neuronsCohort of micePlasma corticosterone levelsPrimary hippocampal neuronsMonths of ageCRF administrationAβ levelsIntraperitoneal injectionHippocampal neurons
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