Featured Publications
PLD3 affects axonal spheroids and network defects in Alzheimer’s disease
Yuan P, Zhang M, Tong L, Morse T, McDougal R, Ding H, Chan D, Cai Y, Grutzendler J. PLD3 affects axonal spheroids and network defects in Alzheimer’s disease. Nature 2022, 612: 328-337. PMID: 36450991, PMCID: PMC9729106, DOI: 10.1038/s41586-022-05491-6.Peer-Reviewed Original ResearchConceptsAxonal spheroidsAlzheimer's diseaseConduction blockadeNeural circuit abnormalitiesNeural network dysfunctionAmyloid removalCircuit abnormalitiesAge-dependent accumulationNetwork dysfunctionEndolysosomal vesiclesMouse modelNeuronal overexpressionCognitive declineAxonal connectivityDiseasePrecise mechanismBlockadePLD3Neural network functionSpheroid growthSevere disruptionCurrent sinkVoltage imagingSize-dependent mannerDysfunctionTREM2 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 fibrilsHaplodeficiencyPlaquesDiseaseDystrophyLifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain
Hill RA, Li AM, Grutzendler J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nature Neuroscience 2018, 21: 683-695. PMID: 29556031, PMCID: PMC5920745, DOI: 10.1038/s41593-018-0120-6.Peer-Reviewed Original ResearchConceptsMyelin degenerationYears of ageAge-related degenerationMyelin plasticityMyelin remodelingNeural processing speedBrain pathogenesisOligodendrocyte deathUnmyelinated axonsAxonal myelinMyelin coverageStructural remodelingMouse cortexMammalian brainPeak myelinationOligodendrocyte generationIndividual axonsMyelinating oligodendrocytesMyelin distributionDegenerationMyelin internodesNetwork homeostasisAxonsStructural plasticityRemodelingLabel-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy
Schain AJ, Hill RA, Grutzendler J. Label-free in vivo imaging of myelinated axons in health and disease with spectral confocal reflectance microscopy. Nature Medicine 2014, 20: 443-449. PMID: 24681598, PMCID: PMC3981936, DOI: 10.1038/nm.3495.Peer-Reviewed Original Research
2019
Uncovering the biology of myelin with optical imaging of the live brain
Hill RA, Grutzendler J. Uncovering the biology of myelin with optical imaging of the live brain. Glia 2019, 67: 2008-2019. PMID: 31033062, PMCID: PMC6744352, DOI: 10.1002/glia.23635.Peer-Reviewed Original Research
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
Thinned-skull cranial window technique for long-term imaging of the cortex in live mice
Yang G, Pan F, Parkhurst CN, Grutzendler J, Gan WB. Thinned-skull cranial window technique for long-term imaging of the cortex in live mice. Nature Protocols 2010, 5: 201-208. PMID: 20134419, PMCID: PMC4690457, DOI: 10.1038/nprot.2009.222.Peer-Reviewed Original ResearchConceptsTwo-photon laser scanning microscopyHigh optical resolutionThinned-skull cranial windowImportant experimental toolOptical resolutionLiving brainCranial window techniqueLive miceLong-term imagingCranial windowExperimental toolInvasive approachAvoids exposureFunctional changesCortical structuresLongitudinal imagingPathological conditionsCortexBrainLaser scanning microscopyScanning microscopyMiceImagingMicroscopyResolution