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 ResearchMeSH KeywordsAlzheimer DiseaseAnimalsComplement C1qDisease Models, AnimalMiceReceptor, Metabotropic Glutamate 5SynapsesConceptsPositron 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
2017
Opposing 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