Association Between Serum Ceruloplasmin Specific Activity and Risk of Alzheimer’s Disease

Article type: Research Article

Authors: Siotto, Mariacristina^{a; *} | Simonelli, Ilaria^b | Pasqualetti, Patrizio^c | Mariani, Stefania^b | Caprara, Deborah^b | Bucossi, Serena^d | Ventriglia, Mariacarla^{b; e} | Molinario, Rossana^f | Antenucci, Mirca^f | Rongioletti, Mauro^g | Rossini, Paolo Maria^{d; h} | Squitti, Rosanna^{b; e}

Affiliations: [a] Don Carlo Gnocchi Foundation ONLUS, Milan, Italy | [b] Fatebenefratelli Foundation for Health Research and Education, AFaR Division, Rome, Italy | [c] Service of Medical Statistics and Information Technology, Fatebenefratelli Foundation for Health Research and Education, AFaR Division, Rome, Italy | [d] Institute of Neurology, Department of Geriatrics, Neuroscience and Orthopedics, Catholic University, Policlinic A. Gemelli, Rome, Italy | [e] Istituto di Scienze e Tecnologie della Cognizione (ISTC) - CNR, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy | [f] Department of Diagnostic and Laboratory Medicine, Catholic University, Policlinic A. Gemelli, Rome, Italy | [g] Molecular Biology Unit, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy | [h] Laboratory of Neurodegeneration, IRCSS “San Raffaele Pisana”, Rome, Italy

Correspondence: [*] Correspondence to: Dr. Mariacristina Siotto, Don Carlo Gnocchi Foundation ONLUS, P.le Morandi 6, 20121 Milan, Italy. Tel.: 06030154435; Fax: 0635501909; E-mail: [email protected].

Abstract: Meta-analyses demonstrate copper involvement in Alzheimer’s disease (AD), and the systemic ceruloplasmin status in relation to copper is an emerging issue. To deepen this matter, we evaluated levels of ceruloplasmin concentration, ceruloplasmin activity, ceruloplasmin specific activity (eCp/iCp), copper, non-ceruloplasmin copper iron, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype in a sample of 84 AD patients and 58 healthy volunteers. From the univariate logistic analyses we found that ceruloplasmin concentration, eCp/iCp, copper, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype were significantly associated with the probability of AD. In the multivariable logistic regression analysis, we selected the best subset of biological predictors by the forward stepwise procedure. The analysis showed a decrease of the risk of having AD for eCp/iCp (p = 0.001) and an increase of this risk for non-ceruloplasmin copper (p = 0.008), age (p = 0.001), and APOE-ɛ4 allele (p <  0.001). The estimated model showed a good power in discriminating AD patients from healthy controls (area under curve: 88% ; sensitivity: 66% ; specificity 93%). These data strength the breakdown of copper homeostasis and propose eCp/iCp as a reliable marker of ceruloplasmin status.

Keywords: Alzheimer’s disease, ceruloplasmin, ceruloplasmin specific activity, non-ceruloplasmin copper

DOI: 10.3233/JAD-150611

Journal: Journal of Alzheimer's Disease, vol. 50, no. 4, pp. 1181-1189, 2016