Elevated labile Cu is associated with oxidative pathology in Alzheimer's disease.
AuthorJAMES, SIMON; VOLITAKIS, IRENE; ADLARD, PAUL; DUCE, JAMES; MASTERS, COLIN; CHERNY, ROBERT; BUSH, ASHLEY
Source TitleFree Radical Biology & Medicine
University of Melbourne Author/sJames, Simon; Volitakis, Irene; Adlard, Paul; Duce, James; Masters, Colin; Cherny, Robert; Bush, Ashley
Access StatusThis item is currently not available from this repository
© 2011 Elsevier Inc. All rights reserved.
Oxidative stress is implicated in Alzheimer disease (AD) pathogenesis, for which evidence indicates that radical species are generated by the redox-active biometal Cu. The contribution of labile Cu to the oxidative stress observed in AD has not been evaluated. The Cu content of postmortem cortical tissue from nondemented elderly controls and AD cases was measured using inductively coupled plasma mass spectroscopy, and the proportion of labile Cu was assessed using the Cu–phenanthroline assay. Further, the capacity of the tissue to stabilize Cu2+ was evaluated using immobilized metal-affinity chromatography, and the level of tissue oxidative damage was determined by the presence of thiobarbituric acid-reactive compounds. We identified elevated levels of exchangeable Cu2+, which were correlated with tissue oxidative damage; additionally, we noted an increased capacity of AD cortical tissue samples to bind Cu2+. This deranged Cu homeostasis reflects the homeostatic breakdown of Cu observed in AD and supports biometal metabolism as a therapeutic target.
Keywordsalzheimer disease; copper; oxidative stress; cortex; metal homeostasis; free radicals
- Click on "Export Reference in RIS Format" and choose "open with... Endnote".
- Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References