%0 Journal Article
%T Decreased Copper in Alzheimer¡¯s Disease Brain Is Predominantly in the Soluble Extractable Fraction
%A Alan Rembach
%A Dominic J. Hare
%A Monica Lind
%A Christopher J. Fowler
%A Robert A. Cherny
%A Catriona McLean
%A Ashley I. Bush
%A Colin L. Masters
%A Blaine R. Roberts
%J International Journal of Alzheimer's Disease
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/623241
%X Alzheimer¡¯s disease (AD) is the leading cause of dementia and represents a significant burden on the global economy and society. The role of transition metals, in particular copper (Cu), in AD has become of significant interest due to the dyshomeostasis of these essential elements, which can impart profound effects on cell viability and neuronal function. We tested the hypothesis that there is a systemic perturbation in Cu compartmentalization in AD, within the brain as well as in the periphery, specifically within erythrocytes. Our results showed that the previously reported decrease in Cu within the human frontal cortex was confined to the soluble ( ) and total homogenate ( ) fractions. No differences were observed in Cu concentration in erythrocytes. Our data indicate that there is a brain specific alteration in Cu levels in AD localized to the soluble extracted material, which is not reflected in erythrocytes. Further studies using metalloproteomics approaches will be able to elucidate the metabolic mechanism(s) that results in the decreased brain Cu levels during the progression of AD. 1. Introduction Alzheimer¡¯s disease (AD) is the predominant cause of dementia in the aging population and represents a mounting health epidemic [1]. Despite advances in understanding the events leading to the onset of cognitive decline, the principal cause of AD is still undetermined. The role of copper (Cu), iron (Fe), and zinc (Zn) in AD has become of significant interest because the dyshomeostasis of essential trace elements has been observed to have profound effects on cell viability and neuronal function [2, 3], which have been previously reviewed [4]. Cu, an essential element in the central nervous system (CNS), is crucial for life, but its unique redox propensity renders it toxic in circumstances of an increase pool of labile species [5¨C8]. Specific lesions in the Cu pathway can lead to a severe but treatable neurological impairment, including Menkes and Wilson¡¯s disease [9¨C11]. Cu displays a distinctly compartmentalized distribution throughout the brain, reflecting its diverse function in various neurological processes [12, 13]. Within the CNS, Cu is known to decrease in the frontal, occipital, and parietal lobes [14] amygdala and hippocampus in AD [15]. The process for this decline is not well understood, though extracellular plaques of aggregated amyloid-¦Â (A¦Â) are reported to be enriched with trace elements including Fe, Zn, and Cu [16]. Recently, it was also reported that frontal cortex from AD subjects had an increased propensity to bind exchangeable Cu,
%U http://www.hindawi.com/journals/ijad/2013/623241/