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

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 (