Free Copper Distinguishes Mild Cognitive Impairment Subjects from Healthy Elderly Individuals

Article type: Research Article

Authors: Squitti, Rosanna^{a; *} | Ghidoni, Roberta^{c; d} | Scrascia, Federica^b | Benussi, Luisa^d | Panetta, Valentina^e | Pasqualetti, Patrizio^{a; f} | Moffa, Filomena^a | Bernardini, Silvia^a | Ventriglia, Mariacarla^{a; b} | Binetti, Giuliano^d | Rossini, Paolo Maria^{a; f}

Affiliations: [a] Department of Neuroscience, AFaR – Osp. Fatebenefratelli, Isola Tiberina, Rome, Italy | [b] Neurology, University “Campus Biomedico”, Rome, Italy | [c] Proteomics Unit, IRCCS “Centro S.Giovanni di Dio-Fatebenefratelli”, Brescia, Italy | [d] NeuroBioGen Lab-Memory Clinic, IRCCS “Centro S.Giovanni di Dio-Fatebenefratelli”, Brescia, Italy | [e] Medical Statistics & Information Technology, AFaR-Fatebenefratelli Association for the Research, Isola Tiberina, Rome, Italy | [f] Epidemiology and Biostatistics, Casa di Cura San Raffaele-Cassino, Italy

Correspondence: [*] Correspondence to: Dr. Rosanna Squitti, PhD, Department of Neuroscience, AFaR – Osp. Fatebenefratelli 00186, Rome, Italy. Tel.: +39 06 6837 385; Fax: +39 06 6837 300; E-mail: [email protected].

Abstract: In patients affected by Alzheimer's disease (AD), serum copper not bound to ceruloplasmin (‘free’ copper) appears elevated, slightly but significantly enough to distinguish AD patients from healthy elderly subjects. In this paper we tested the hypothesis that this is also the case for individuals affected by mild cognitive impairment (MCI). A sample of 83 MCI subjects were compared with 100 elderly control subjects in terms of levels of serum copper, free copper, ceruloplasmin, apolipoprotein E4 genotype (APOE4), iron, transferrin, and total antioxidant capacity (TRAP). The groups were also compared in terms of demographic and cardiovascular risk factors. The comparison with an additional group of 105 mild to moderate AD patients was also evaluated. The possible effects of copper dysfunction on cognitive decline were evaluated by multinomial logistic regression analysis. A linear regression model was applied to define the role of metals and antioxidant dysfunction in explaining Mini-Mental Status Examination (MMSE) variations. APOE4 and free copper differentiated the MCI group from the healthy control group. The probability of aquiring MCI increased by about 24% for each free copper unit (μmol/L) increment. APOE4 and free copper differentiated the MCI group also from the AD group. APOE4 and free copper appeared associated to MMSE worsening, as did age and gender. These results suggest that free copper can help in discriminating MCI subjects from healthy controls, but not on an individual basis.

Keywords: Alzheimer's disease, apolipoprotein E, copper, mild cognitive impairment

DOI: 10.3233/JAD-2010-101098

Journal: Journal of Alzheimer's Disease, vol. 23, no. 2, pp. 239-248, 2011