26 Copper Failure in Wilson and Alzheimer Disease

Abstract

Copper failure is the cause of Wilson disease (WD), a rare disorder typified by increased levels of copper nonbound to ceruloplasmin (non-Cp Cu) and copper-ceruloplasmin ratio (Cu:Cp). Meta-analyses also show copper abnormalities in Alzheimer disease (AD); however, a direct comparison of copper biological status in the two diseases has never been carried out. An investigation of copper status in serum (copper, ceruloplasmin, non-Cp Cu and Cu:Cp, adjusting for sex and age) and a 24-hour copper urine assessment of patients with AD, WD (nine WD patients at baseline and 24 WD patients under D-penicillamine [D-pen] treatment)], and healthy controls (35 healthy controls) was carried out. In a sample of 385 AD cases and 336 healthy controls investigated in previous studies, non-Cp Cu and Cu:Cp were higher in AD than healthy controls (both P < .001), but lower than in WD patients at baseline. While non-Cp Cu was similar in AD and WD, mean value of Cu:Cp distinguished AD from WD (P < .016), with the Cu:Cp Cohen d value of 0.8 (indicating a large biological effect) in AD vs healthy controls, which further increases in WD to 2.2. Concentrations of 24-hour urine copper in 35 healthy controls were compared with those at baseline of an AD patient group analyzed in a previous study on the effect of D-pen on the disease progression. AD patients at baseline had higher concentrations of 24-hour urine copper (P < .001; AD 12.05 µg/day [median, interquartile range 7.85–22.50]) than healthy controls (4.82 µg/day (median, interquartile range: 3.31–7.43]). Values of 24-hour urine copper higher than the cutoff of 200 µg/day were found in 87% of WD and 78% of AD. The direct comparison of AD and WD patients shows a copper failure affecting both diseases, but at a different degree, with the Cu:Cp signifying a more severe grade in WD.