Featured Publications
Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
Condello C, Yuan P, Grutzendler J. Microglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging. Biological Psychiatry 2017, 83: 377-387. PMID: 29169609, PMCID: PMC5767550, DOI: 10.1016/j.biopsych.2017.10.007.Peer-Reviewed Original ResearchConceptsAlzheimer's diseasePlaque compactionAmyloid depositsInvolvement of microgliaPlaque-associated microgliaLate-onset Alzheimer's diseaseMyeloid cells 2Onset Alzheimer's diseaseMicroglia receptorMicroglia polarizationAD neuropathologyAxonal pathologyNeuroprotective functionDisease progressionOptical imaging studiesCurrent evidenceAD riskMicrogliaTherapeutic targetingAdjacent axonsImaging studiesCells 2DiseasePrecise mechanismRecent genetic studiesATP mediates rapid microglial response to local brain injury in vivo
Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB. ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience 2005, 8: 752-758. PMID: 15895084, DOI: 10.1038/nn1472.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsApyraseAstrocytesBrainBrain InjuriesCell CommunicationChemotaxisConnexinsGliosisGreen Fluorescent ProteinsMiceMice, TransgenicMicrogliaPhagocytosisPurinergic P2 Receptor AntagonistsReaction TimeReceptors, Purinergic P2Receptors, Purinergic P2Y1Signal TransductionConceptsRapid microglial responseMicroglial processesMicroglial responseBrain injuryG protein-coupled purinergic receptorsLocal brain injuryTraumatic brain injurySite of injuryPrincipal immune cellsPresence of apyraseParenchymal microgliaImmune cellsLocal injectionPurinergic receptorsBaseline motilityIntact brainTwo-photon imagingChannel inhibitorsMouse cortexInjuryExtracellular ATPMicrogliaEnzyme apyraseAstrocytesChemotactic responseMicroglia 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
TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques
Wang Y, Ulland TK, Ulrich JD, Song W, Tzaferis JA, Hole JT, Yuan P, Mahan TE, Shi Y, Gilfillan S, Cella M, Grutzendler J, DeMattos RB, Cirrito JR, Holtzman DM, Colonna M. TREM2-mediated early microglial response limits diffusion and toxicity of amyloid plaques. Journal Of Experimental Medicine 2016, 213: 667-675. PMID: 27091843, PMCID: PMC4854736, DOI: 10.1084/jem.20151948.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseTREM2 deficiencyAβ accumulationNeuritic damageAβ plaquesMyeloid cellsAbsence of TREM2Impact of TREM2Rare TREM2 variantsAmyloid β accumulationBrain-resident microgliaMyeloid cells 2Peripheral blood monocytesEarly time pointsMicroglial clusteringMicroglial receptorΒ accumulationAβ depositsNeuronal degenerationTREM2 variantsAmyloid plaquesMurine modelBlood monocytesMatter of debateMicroglia
2011
Transcranial Two-Photon Imaging of the Living Mouse Brain
Grutzendler J, Yang G, Pan F, Parkhurst CN, Gan WB. Transcranial Two-Photon Imaging of the Living Mouse Brain. Cold Spring Harbor Protocols 2011, 2011: pdb.prot065474. PMID: 21880826, PMCID: PMC4641516, DOI: 10.1101/pdb.prot065474.Peer-Reviewed Original ResearchConceptsMouse brainAxonal varicositiesSurgical proceduresDendritic spinesSide effectsBrain cellsTwo-photon imagingInvasive methodBlood vesselsSame animalsPathological conditionsTwo-photon microscopyIntact skullBrainTranscranialImagingMicrogliaSurgeryVaricositiesImaging methodNeuronsLong time intervalsSpine
2010
CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis
Liu Z, Condello C, Schain A, Harb R, Grutzendler J. CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis. Journal Of Neuroscience 2010, 30: 17091-17101. PMID: 21159979, PMCID: PMC3077120, DOI: 10.1523/jneurosci.4403-10.2010.Peer-Reviewed Original ResearchConceptsCX3CR1-deficient miceAlzheimer's diseaseAmyloid-β PhagocytosisBrain amyloid depositionLower brain levelsGreater phagocytic capacityQuantification of AβHigh proliferative rateAβ phagocytosisActivated microgliaMicroglia activationMicroglia activityAmyloid pathologyAmyloid depositionMicroglia densityBrain levelsPlaque depositionSynaptic damageChemokine receptorsDisease progressionMicrogliaTherapeutic strategiesAmyloid depositsPhagocytic capacityPhagocytic ability