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 studiesTREM2 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 fibrilsHaplodeficiencyPlaquesDiseaseDystrophy
2015
Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer’s disease amyloid plaques
Gowrishankar S, Yuan P, Wu Y, Schrag M, Paradise S, Grutzendler J, De Camilli P, Ferguson SM. Massive accumulation of luminal protease-deficient axonal lysosomes at Alzheimer’s disease amyloid plaques. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e3699-e3708. PMID: 26124111, PMCID: PMC4507205, DOI: 10.1073/pnas.1510329112.Peer-Reviewed Original ResearchConceptsAmyloid plaquesNeuronal lysosomesAlzheimer's diseaseAlzheimer's disease brain pathologyLysosome accumulationAlzheimer's disease (AD) amyloid plaquesΒ-amyloid depositionΒ-amyloid depositsAmyloid precursor proteinLysosome-like organellesRetrograde axonal transportWild-type brainsSuch axonsSwollen axonsMassive accumulationAxonal lysosomesBrain pathologyAmyloidogenic processingMouse modelAmyloid depositsLuminal proteasesAxonal transportLocal impairmentNeuronal processesNeurodegenerative diseases
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
2007
Various Dendritic Abnormalities Are Associated with Fibrillar Amyloid Deposits in Alzheimer's Disease
GRUTZENDLER J, HELMIN K, TSAI J, GAN W. Various Dendritic Abnormalities Are Associated with Fibrillar Amyloid Deposits in Alzheimer's Disease. Annals Of The New York Academy Of Sciences 2007, 1097: 30-39. PMID: 17413007, DOI: 10.1196/annals.1379.003.Peer-Reviewed Original ResearchConceptsAmyloid depositsAlzheimer's diseasePSAPP miceFibrillar amyloid depositsAmyloid depositionDendritic abnormalitiesHuman AD tissueFibrillar amyloid depositionHuman AD brainsTransgenic mouse modelHuman postmortem brainDystrophic neuritesSpine lossAD brainAD tissueAmyloid plaquesCommon abnormalityMouse modelPostmortem brainsDendritic spinesNeuronal circuitsVaricosity formationSynaptic structureDiseaseDendritic branches
2004
Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches
Tsai J, Grutzendler J, Duff K, Gan WB. Fibrillar amyloid deposition leads to local synaptic abnormalities and breakage of neuronal branches. Nature Neuroscience 2004, 7: 1181-1183. PMID: 15475950, DOI: 10.1038/nn1335.Peer-Reviewed Original ResearchConceptsFibrillar amyloid depositionAmyloid depositionAlzheimer's diseaseTransgenic mouse modelImportance of preventionFibrillar amyloid depositsSpine lossNearby axonsNeuronal labelingEarly clearanceLarge varicositiesAmyloid plaquesMouse modelNeuronal circuitryAmyloid depositsTwo-photon imagingNeuronal connectionsSynaptic abnormalitiesNeuronal branchesPermanent disruptionPlaquesDiseaseAtrophyVaricositiesPathogenesis