Copper dyshomeostasis in Wilson disease and Alzheimer's disease as shown by serum and urine copper indicators

Rosanna Squitti, Roberta Ghidoni, Ilaria Simonelli, Irena D Ivanova, Nicola Antonio Colabufo, Massimo Zuin, Luisa Benussi, Giuliano Binetti, Emanuele Cassetta, Mauro Rongioletti, Mariacristina Siotto

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Abstract

Abnormal handling of copper is the cause of Wilson disease (WD), a rare disorder typified by increased levels in plasma copper not-bound to ceruloplasmin (nCp-Cu, also known as 'free' copper). In Alzheimer's disease (AD), meta-analyses show that copper decreases in brain but increases in serum, due to the nCp Cu component increase. Despite the similarities, a direct comparison of copper biological status in the two diseases has never been carried out. To fill this gap, we evaluated serum copper, ceruloplasmin, nCp-Cu and Cu:Cp in 385 CE and 336 healthy controls previously investigated that were compared with 9 newly diagnosed WD patients. We then assessed 24h copper urinary excretion in 24 WD patients under D-penicillamine (D-pen) treatment and in 35 healthy controls, and compared results with those of AD patients participating to a D-pen phase II clinical trial previously published. After adjusting for sex and age, serum nCp-Cu and Cu:Cp resulted higher in AD and in WD than in healthy controls (both p<0.001). While nCp-Cu was similar between AD and WD, Cu:Cp was higher in WD (p<0.016). 24h urinary copper excretion in AD patients (12.05μg/day) was higher than in healthy controls (4.82μg/day; p<0.001). 77.8% of the AD patients under D-pen treatment had a 24h urinary excretion higher than 200μg/day, suggestive of a failure of copper control. This study provides new insight into the pathophysiology of copper homeostasis in AD, showing a failure of copper control and the Cu:Cp ratio as an eligible marker.

Original languageEnglish
Pages (from-to)Epub Ahead of Print
Number of pages8
JournalJournal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
Volume45
DOIs
Publication statusE-pub ahead of print - 2017

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