ATP7B variants as modulators of copper dyshomeostasis in Alzheimer's disease

Rosanna Squitti, Renato Polimanti, Mariacristina Siotto, Serena Bucossi, Mariacarla Ventriglia, Stefania Mariani, Fabrizio Vernieri, Federica Scrascia, Laura Trotta, Paolo Maria Rossini

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)515-522
Number of pages8
JournalNeuroMolecular Medicine
Issue number3
Publication statusPublished - Sep 2013


  • Alzheimer's disease
  • ATP7B
  • Ceruloplasmin
  • Copper
  • Wilson's disease

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Medicine
  • Neurology


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