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
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