title: Elevated labile Cu is associated with oxidative pathology in Alzheimer disease.
abstract: 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 Cu(2+) 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 Cu(2+), which were correlated with tissue oxidative damage; additionally, we noted an increased capacity of AD cortical tissue samples to bind Cu(2+). This deranged Cu homeostasis reflects the homeostatic breakdown of Cu observed in AD and supports biometal metabolism as a therapeutic target.
authors.affiliation: The Mental Health Research Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.
authors.forename: Simon A
authors.initials: SA
authors.lastname: James
authors.forename: Irene
authors.initials: I
authors.lastname: Volitakis
authors.forename: Paul A
authors.initials: PA
authors.lastname: Adlard
authors.forename: James A
authors.initials: JA
authors.lastname: Duce
authors.forename: Colin L
authors.initials: CL
authors.lastname: Masters
authors.forename: Robert A
authors.initials: RA
authors.lastname: Cherny
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D056831:Coordination Complexes / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D005260:Female; D006706:Homeostasis; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D013054:Spectrophotometry, Atomic; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D015415:Biomarkers; D056831:Coordination Complexes; D017392:Thiobarbituric Acid Reactive Substances; D003300:Copper