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

• Published in: Journal of Trace Elements in Medicine and Biology Vol. 45; pp. 181 - 188
• Main Authors: Squitti, Rosanna, Ghidoni, Roberta, Simonelli, Ilaria, Ivanova, Irena D., Colabufo, Nicola Antonio, Zuin, Massimo, Benussi, Luisa, Binetti, Giuliano, Cassetta, Emanuele, Rongioletti, Mauro, Siotto, Mariacristina
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.01.2018; Elsevier BV
• Subjects: Alzheimer Disease; Alzheimer Disease - blood; Alzheimer Disease - urine; Alzheimer's disease; Ceruloplasmin; Copper; Copper - blood; Copper - urine; Cu:Cp; Female; Hepatolenticular Degeneration; Hepatolenticular Degeneration - blood; Hepatolenticular Degeneration - urine; Humans; Male; Urine; Wilson disease; Ceruloplasmin; Urine; Cu:Cp; Wilson disease; Copper; Alzheimer's disease
• ISSN: 0946-672X; 1878-3252; 1878-3252
• DOI: 10.1016/j.jtemb.2017.11.005

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.