title: Ceruloplasmin fragmentation is implicated in 'free' copper deregulation of Alzheimer's disease.
abstract: A dysfunction in copper homeostasis seems to occur in Alzheimer's disease (AD). We recently demonstrated that an excess of non-ceruloplasmin-copper (i.e., 'free' copper) correlates with the main functional and anatomical deficits as well as the cerebrospinal markers of the disease, thus suggesting that copper contributes to AD neurodegeneration. Aim of this study was to investigate the profile of serum ceruloplasmin isoforms immunoreactive protein in relation to copper dysfunction in AD. Twenty-five AD patients and 25 controls were included in the study. All subjects underwent individual measurements of serum ceruloplasmin and copper concentrations, and the amount of 'free' copper was computed for each copper and ceruloplasmin pair. Serum samples were also pooled and analyzed by two dimensional polyacrylamide gel electrophoresis (2-D PAGE) and western blot analysis. The mean concentration of 'free' copper resulted higher in AD patients than in controls. Ceruloplasmin 2-D PAGE western blot analysis of pooled sera showed in the AD samples low-molecular-weight spots in the <50 kDa range that were not detected in controls' pooled sera (p < 0.029). Our data indicate a ceruloplasmin fragmentation in the serum of AD patients, possibly related to 'free' copper deregulation in this disease.
authors.affiliation: AfaR, Department of Neuroscience, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy. rosanna.squitti@afar.it
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
authors.forename: Carlo C
authors.initials: CC
authors.lastname: Quattrocchi
authors.forename: Carlo
authors.initials: C
authors.lastname: Salustri
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Rossini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D002570:Ceruloplasmin / Q000378:metabolism*; D003300:Copper / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male
chemical_list: D003300:Copper; D002570:Ceruloplasmin