Featured Publications
TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy
Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM, Luo W, Colonna M, Baddeley D, Grutzendler J. TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. Neuron 2016, 90: 724-739. PMID: 27196974, PMCID: PMC4898967, DOI: 10.1016/j.neuron.2016.05.003.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseAxonal dystrophyAmyloid depositsAD-like miceHuman AD tissueLate-onset Alzheimer's diseaseNovel therapeutic strategiesTREM2 deficiencyTau hyperphosphorylationAD tissueMicroglia processesPharmacological modulationCompact plaquesTherapeutic strategiesHigh-resolution confocalTREM2 mutationsTREM2Barrier functionMiceGreater surface exposureAmyloid fibrilsHaplodeficiencyPlaquesDiseaseDystrophyTREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy
Yuan P, Condello C, Keene CD, Wang Y, Bird TD, Paul SM, Luo W, Colonna M, Baddeley D, Grutzendler J. TREM2 Haplodeficiency in Mice and Humans Impairs the Microglia Barrier Function Leading to Decreased Amyloid Compaction and Severe Axonal Dystrophy. Neuron 2016, 92: 252-264. PMID: 27710785, DOI: 10.1016/j.neuron.2016.09.016.Peer-Reviewed Original ResearchMicroglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques
Condello C, Yuan P, Schain A, Grutzendler J. Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques. Nature Communications 2015, 6: 6176. PMID: 25630253, PMCID: PMC4311408, DOI: 10.1038/ncomms7176.Peer-Reviewed Original Research
2016
Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity
Yuan P, Grutzendler J. Attenuation of β-Amyloid Deposition and Neurotoxicity by Chemogenetic Modulation of Neural Activity. Journal Of Neuroscience 2016, 36: 632-641. PMID: 26758850, PMCID: PMC4710779, DOI: 10.1523/jneurosci.2531-15.2016.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCalcium-Binding ProteinsClozapineDesigner DrugsDisease Models, AnimalHumansInsulysinLysosome-Associated Membrane GlycoproteinsMaleMiceMice, TransgenicMicrofilament ProteinsNerve Tissue ProteinsNeurotoxicity SyndromesPresenilin-1Proto-Oncogene Proteins c-fosStyrenesTransduction, GeneticConceptsAmyloid plaquesAlzheimer's diseaseNeuronal activityAmyloid depositionDisease miceNeural activityAD-like mouse modelNeural activity reductionΒ-amyloid depositionAlzheimer's disease miceNovel therapeutic approachesPotential therapeutic strategyViral-mediated deliveryChemogenetic modulationSynaptic lossAβ depositionSynaptic pathologyNeural hyperactivityAmyloid pathologyAxonal dystrophyDendritic fieldsChronic attenuationDesigner receptorsTherapeutic approachesMouse model