Value of serum nonceruloplasmin copper for prediction of mild cognitive impairment conversion to Alzheimer disease

Rosanna Squitti, Roberta Ghidoni, Mariacristina Siotto, Mariacarla Ventriglia, Luisa Benussi, Anna Paterlini, Mariachiara Magri, Giuliano Binetti, Emanuele Cassetta, Deborah Caprara, Fabrizio Vernieri, Paolo M. Rossini, Patrizio Pasqualetti

Research output: Contribution to journalArticlepeer-review


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 >1.6μmol/l had a hazard conversion rate (50% of conversion in 4 years) that was ∼3× higher than those with values ≤1.6μmol/l (

Original languageEnglish
Pages (from-to)574-580
Number of pages7
JournalAnnals of Neurology
Issue number4
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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