Rosanna Squitti¹, Carlo C. Quattrocchi², Gloria Dal Forno³, Piero Antuono⁴, David R. Wekstein⁵, Concetta R. Capo⁶, Carlo Salustri⁷ and Paolo M. Rossini1^3,8

¹AFaR, Dept. of Neuroscience, Fatebenefratelli Hospital, Rome, Italy. ²Depts. of Radiology "Campus Biomedico" University, Rome, Italy. ³Depts. of Neurology, "Campus Biomedico" University, Rome, Italy. ⁴Dept. of Neurology, Medical College of Wisconsin, Milwaukee, WI, U.S.A. ⁵University of Kentucky Alzheimer's Disease Research Center, Lexington, KY, U.S.A. ⁶Dept. of Biology, Tor Vergata University, Rome, Italy. ⁷Institute of Cognition Sciences and Technologies (CNR), Rome, Italy. ⁸IRCCS ‘Centro S. Giovanni di Dio-FBF', Brescia, Italy.

Abstract: A dysfunction in copper homeostasis seems to occur in Alzheimer's disease (AD). We previously evidenced that an excess of non-ceruloplasmin-copper (NCC) correlated with the main functional, anatomical as well as cerebrospinal markers of the disease. Aim of our study was to investigate ceruloplasmin isoforms as potential actors in this AD copper dysfunction. Our data show that AD patients have ceruloplasmin fragments of low molecular weight (<50 kDa) both in their serum and brain, contrary to healthy controls. Ceruloplasmin isoforms of higher molecular weight (115 and 135 kDa in serum and 135 kDa in brain), as well as copper levels in the brain, instead, do not seem to mark a difference between AD and healthy subjects. These data suggest a ceruloplasmin fragmentation in the serum of AD patients. Some clues in this direction have been found also in the AD brain.