title: Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease.
abstract: OBJECTIVE
  Meta-analyses show that nonbound ceruloplasmin (non-Cp) copper (also known as free or labile copper) in serum is higher in patients with Alzheimer disease (AD). It differentiates subjects with mild cognitive impairment (MCI) from healthy controls. However, a longitudinal study on an MCI cohort has not yet been performed to assess the accuracy of non-Cp copper for the prediction of conversion from MCI to AD during a long-term follow-up.
  
  
  METHODS
  The study included 42 MCI converters and 99 stable MCI subjects. We assessed levels of copper, ceruloplasmin, non-Cp copper, iron, transferrin, ferritin, and APOE genotype. A multiple Cox regression analysis-with age, sex, baseline Mini-Mental State Examination, APOE4, iron, non-Cp copper, transferrin, ferritin, hypercholesterolemia, and hypertension as covariates-was applied to predict the conversion from MCI to AD.
  
  
  RESULTS
  Among the evaluated parameters, the only significant predictor of conversion to AD was non-Cp copper (hazard ratio = 1.23, 95% confidence interval = 1.03-1.47, p = 0.022); for each additional micromole per liter unit (μmol/l) of non-Cp copper, the hazard increased by ~20%. Subjects with non-Cp copper levels >1.6 μmol/l had a hazard conversion rate (50% of conversion in 4 years) that was ~3× higher than those with values ≤1.6 μmol/l (<20% in 4 years). The rate of conversion was similar between APOE4 carriers and noncarriers (p = 0.321), indicating that the non-Cp copper association was independent of APOE4.
  
  
  CONCLUSIONS
  Non-Cp copper appears to predict conversion from MCI to AD. These results encourage healthy life style choices and dietary intervention to modify this risk.
authors.affiliation: Department of Neuroscience, Fatebenefratelli Foundation, AFaR Division, Fatebenefratelli Hospital, Isola Tiberina, Rome; Laboratory of Neurodegeneration, IRCCS "San Raffaele Pisana", Rome.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
authors.forename: Roberta
authors.initials: R
authors.lastname: Ghidoni
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Siotto
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Ventriglia
authors.forename: Luisa
authors.initials: L
authors.lastname: Benussi
authors.forename: Anna
authors.initials: A
authors.lastname: Paterlini
authors.forename: Mariachiara
authors.initials: M
authors.lastname: Magri
authors.forename: Giuliano
authors.initials: G
authors.lastname: Binetti
authors.forename: Emanuele
authors.initials: E
authors.lastname: Cassetta
authors.forename: Deborah
authors.initials: D
authors.lastname: Caprara
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vernieri
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Rossini
authors.forename: Patrizio
authors.initials: P
authors.lastname: Pasqualetti
mesh_terms: D000544:Alzheimer Disease / Q000097:blood* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D002570:Ceruloplasmin / Q000378:metabolism; D003072:Cognition Disorders / Q000097:blood* / Q000235:genetics; D003300:Copper / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009483:Neuropsychological Tests; D011237:Predictive Value of Tests; D011336:Probability; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D003300:Copper; D002570:Ceruloplasmin