TY - JOUR
T1 - ATP7B variants as modulators of copper dyshomeostasis in Alzheimer's disease
AU - Squitti, Rosanna
AU - Polimanti, Renato
AU - Siotto, Mariacristina
AU - Bucossi, Serena
AU - Ventriglia, Mariacarla
AU - Mariani, Stefania
AU - Vernieri, Fabrizio
AU - Scrascia, Federica
AU - Trotta, Laura
AU - Rossini, Paolo Maria
PY - 2013
Y1 - 2013
N2 - To understand the role of the key copper-regulating gene, ATP7B, in copper dyshomeostasis associated with Alzheimer's disease (AD), we analyzed the serum levels of copper, ceruloplasmin and 'free' (i.e., non-ceruloplasmin bound) copper in 399 patients with AD and 303 elderly healthy controls. We also performed analyses of informative variants of ATP7B. AD patients had higher levels of copper and free copper than controls. Individuals with free copper levels higher than 1.6 μmol/L (the upper value of the normal reference range) were more frequent among cases (p < 0.001). Among these individuals, those who were carriers of the ATP7B variants accounted for a large proportion of the free copper levels, specifically in the AD group (p < 0.01). Our results suggest the existence of a 'copper dysfunction' phenotype of sporadic AD which has a genetic basis. They also suggest that free copper is a risk factor for this disorder, modulating additional pathways leading to the disease cascade.
AB - To understand the role of the key copper-regulating gene, ATP7B, in copper dyshomeostasis associated with Alzheimer's disease (AD), we analyzed the serum levels of copper, ceruloplasmin and 'free' (i.e., non-ceruloplasmin bound) copper in 399 patients with AD and 303 elderly healthy controls. We also performed analyses of informative variants of ATP7B. AD patients had higher levels of copper and free copper than controls. Individuals with free copper levels higher than 1.6 μmol/L (the upper value of the normal reference range) were more frequent among cases (p < 0.001). Among these individuals, those who were carriers of the ATP7B variants accounted for a large proportion of the free copper levels, specifically in the AD group (p < 0.01). Our results suggest the existence of a 'copper dysfunction' phenotype of sporadic AD which has a genetic basis. They also suggest that free copper is a risk factor for this disorder, modulating additional pathways leading to the disease cascade.
KW - inglese
KW - inglese
UR - http://hdl.handle.net/10807/53828
U2 - 10.1007/s12017-013-8237-y
DO - 10.1007/s12017-013-8237-y
M3 - Article
SN - 1535-1084
VL - 15
SP - 515
EP - 522
JO - NeuroMolecular Medicine
JF - NeuroMolecular Medicine
ER -