Longitudinal Analysis of Serum Copper and Ceruloplasmin in Alzheimer's Disease

Article type: Research Article

Authors: Rembach, Alan^{a; c} | Doecke, James D.^{b; c; d} | Roberts, Blaine R.^a | Watt, Andrew D.^a | Faux, Noel G.^a | Volitakis, Irene^a | Pertile, Kelly K.^a | Rumble, Rebecca L.^a | Trounson, Brett O.^a | Fowler, Christopher J.^a | Wilson, William^{c; d} | Ellis, Kathryn A.^{a; e; h} | Martins, Ralph N.^f | Rowe, Christopher C.^g | Villemagne, Victor L.^{a; g} | Ames, David^h | Masters, Colin L^a | AIBL research groupⁱ | Bush, Ashley I.^{a; *}

Affiliations: [a] The Mental Health Research Institute, The University of Melbourne, VIC, Australia | [b] The Australian e-Health Research Centre, Herston, QLD, Australia | [c] CSIRO Preventative Health Flagship, Molecular Science and Engineering, Parkville, VIC, Australia | [d] CSIRO Mathematics and Information Sciences, Macquarie University, QLD, Australia | [e] Department of Psychiatry, St George's Hospital, University of Melbourne, VIC, Australia | [f] Sir James McCusker Alzheimer's Disease Research Unit, Health Department of WA, Perth, WA, Australia | [g] Department of Nuclear Medicine and Centre for PET, Austin Health, Heidelberg, VIC, Australia | [h] National Ageing Research Institute, Parkville, VIC, Australia | [i] http://www.aibl.csiro.au/

Correspondence: [*] Correspondence to: Professor Ashley I. Bush, The Mental Health Research Institute, Kenneth Myer Building, 30 Royal Parade, Parkville, VIC 3010, Australia. Tel.: +61 3 9035 6532; Fax: +61 3 9035 8642; E-mail: [email protected].

Abstract: Background:Several studies have reported that peripheral levels of copper and ceruloplasmin (CP) can differentiate patients with Alzheimer’s disease (AD) from non-AD cases. The aim of this study was to determine the diagnostic value of serum copper, CP, and non-CP copper levels in a large cohort of AD subjects. Methods:Serum copper and CP concentrations were measured at baseline and at 18-months in participants from the Australian Imaging Biomarkers and Lifestyle Study of Ageing. Cross-sectional and longitudinal analyses were conducted using both univariate and multivariate testing adjusting for age, gender, total protein, and ApoE ε4 genotype status. Results:There was no significant difference in levels of serum copper or CP between the AD and healthy control groups, however, we identified a near-significant decrease in non-CP copper in the mild cognitive impairment and AD groups at baseline (p = 0.02) that was significant at 18-months (p = 0.003). Conclusion:Our results suggest that there may be decreased non-CP copper levels in mild cognitive impairment and AD, which is consistent with diminished copper-dependent biochemical activities described in AD.

Keywords: Alzheimer's disease, biomarkers, ceruloplasmin, copper, serum

DOI: 10.3233/JAD-121474

Journal: Journal of Alzheimer's Disease, vol. 34, no. 1, pp. 171-182, 2013