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J Trace Elem Med Biol. 2018 Jan;45:181-188. doi: 10.1016/j.jtemb.2017.11.005. Epub 2017 Nov 8.

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

Author information

1
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy. Electronic address: rosanna.squitti@afar.it.
2
Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy.
3
Fatebenefratelli Foundation, AFaR Division, Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy.
4
Clinical Laboratory Department, St. Ivan Rilski University Hospital, Medical University, Sofia, Bulgaria.
5
Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "A. Moro, Bari, Italy.
6
Unit San Paolo School of Medicine Department of Health Sciences, University of Milan, Italy.
7
MAC Memory Center, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
8
Department of Laboratory Medicine, Research and Development Division, 'San Giovanni Calibita', Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy.
9
Don Carlo Gnocchi ONLUS Foundation, Milan, Italy.

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.

KEYWORDS:

Alzheimer's disease; Ceruloplasmin; Copper; Cu:Cp; Urine; Wilson disease

PMID:
29173477
DOI:
10.1016/j.jtemb.2017.11.005
[Indexed for MEDLINE]

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