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| 1 | Modulation of tau phosphorylation by environmental copper显示文摘Background:The transition metal copper enhances amyloidβaggregation and neurotoxicity,and in models of concomitant amyloid and tau pathology,copper also promotes tau aggregation.Since it is not clear if the effects of environmental copper upon tau pathology are dependent on the presence of pathological amyloidβ,we tested the effects of copper overload and complexing in disease models which lack pathological amyloidβ.Methods:We used cell culture and transgenic murine models to test the effects of environmental copper on tau phosphorylation.We used oral zinc acetate as a copper lowering agent in mice and examined changes in blood and brain metals through inductively coupled plasma mass spectroscopy.Behavioral effects of copper lowering were assessed with Morris water maze and novel object recognition tasks.Changes in tau phosphorylation were examined by phosphorylation specific antibodies on Western blots.Results:In human neuroblastoma cells,excess copper promoted tau phosphorylation and a copper complexing agent,tetrathiomolybdate,attenuated tau phosphorylation.In a transgenic mouse model expressing wild type human tau,copper-lowering by oral zinc suppressed plasma and brain levels of copper,and resulted in a marked attenuation of tau phosphorylation.No significant changes in behavior were observed with copper lowering,but a trend to improved recognition of the novel object was observed in zinc acetate treated mice.Conclusions:We propose that reduction of brain copper by blocking uptake of copper from the diet may be a viable strategy for modulating tau pathology in Alzheimer’s disease.The potential benefits of this approach are tempered by the absence of a behavioral benefit and by the health risks of excessive lowering of copper. | Kellen Voss Christopher Harris Martina Ralle Megan Duffy Charles Murchison Joseph F Quinn | 2014 | Translational Neurodegeneration2014，3，1： | 3 |
| 2 | Randomized, double-blind, placebo-controlled trial of intravenous ketamine in acute asthma 显示文摘 | John Rose Scott Duffy | 1996 | Ann Emerg Med1996，27，： | 1 |
| 3 | An optimization approach to the determination of the boundaries of manipulator workspaces显示文摘 | Snyman J A du Plessis L J Joseph Duffy | 2000 | Journal of Mechanical Design Transactions of the ASME2000，122，： | 1 |
| 4 | Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech 显示文摘 | Josephs KA Duffy JR Strand EA etal | 2006 | Brain2006，129，： | 1 |
| 5 | Progressive aphasia secondary to Alzheimer disease vs FrLD pathology 显示文摘 | Josephs KA Whitwell JL Duffy JR eta1 | 2008 | Neur- ology2008，70，1： | 1 |
| 6 | Pharmacological Concentrations of Ascorbic Acid Are Required for the Beneficial Effect on Endothelial Vasomotor Function in Hypertension显示文摘 | Debra L. Sherman John F. Keaney Elizabeth S. Biegelsen Stephen J. Duffy Jay D. Coffman Joseph A. Vita | 2000 | Hypertension: Journal of the American Heart Association2000，，4： | 1 |
| 7 | Progres- sive aphasia secondary to Alzheimer disease vs FTLD pathology显示文摘 | Josephs KA Whitwell JL Duffy JR | 2008 | Neurology2008，70，1： | 1 |
| 8 | Forward and inverse accel eration analyses of in-parallel manipulators 显示文摘 | José María Rartínez Joseph Duffy | 2000 | ASME J of Mechannical Design2000，122，： | 1 |
| 9 | Treatment of hypertension with ascorbic acid显示文摘 | StephenJ Duffy Noyan Gokce Monika Holbrook Annong Huang Balz Frei John F Keaney Joseph A Vita | 1999 | The Lancet1999，，9195： | 1 |
| 10 | Clinicopathological and imaging correlates of progressive aphasia and apraxia of speech 显示文摘 | Josephs KA Duffy JR Strand EA | 2006 | Brain2006，129，6： | 1 |
| 11 | Effect of atorvastatin on endothelium-dependent vasodilation in patients with coronary artery disease显示文摘 | Joseph A Vita Noyan Gokce Stephen J Duffy David Kahn Douglas Tomasian Joseph Palmisano Shane Thomas Monika Holbrook John F Keaney | 2003 | The American Journal of Cardiology2003，，7： | 1 |
| 12 | Progranulin-associated PiB-negative logopenic primary progressive aphasia显示文摘 | Josephs KA Duffy JR Strand EA | 2014 | J Neurol2014，261，60： | 1 |
| 13 | Muhicast-based loss inference with missing data显示文摘 | Duffied N Joseph H Don T | 2002 | IEEE Journal on Selected Areas in Communications2002，20，4： | 1 |
| 14 | Muhicast-based loss inference with missing data显示文摘 | DUFFIED N JOSEPH H DON T | 2002 | IEEE Journal on Selected Areas in Com munications2002，20，4： | 1 |
| 15 | Atypical progressive supranuclear palsy underlying progressive apraxia of speech and nonfluent aphasia显示文摘 | Josephs KA Boeve BF Duffy JR | 2005 | Neurocase2005，11，4： | 1 |
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