2021
Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model
Zhou HJ, Qin L, Jiang Q, Murray KN, Zhang H, Li B, Lin Q, Graham M, Liu X, Grutzendler J, Min W. Caveolae-mediated Tie2 signaling contributes to CCM pathogenesis in a brain endothelial cell-specific Pdcd10-deficient mouse model. Nature Communications 2021, 12: 504. PMID: 33495460, PMCID: PMC7835246, DOI: 10.1038/s41467-020-20774-0.Peer-Reviewed Original ResearchConceptsCerebral cavernous malformationsCCM lesionsSmooth muscle actin-positive pericytesEndothelial cell lossRegions of brainCCM pathogenesisPost-capillary venulesCerebral hemorrhagePharmacological blockadeVascular abnormalitiesEC-specific deletionCavernous malformationsMouse modelCell lossMicrovascular bedGenetic deletionLesion formationLesionsVascular dynamicsBarrier functionMicrovascular structureTwo-photon microscopyTie2PathogenesisMice
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
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