NeuroMolecular Medicine

, Volume 15, Issue 3, pp 515–522

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
Original Paper

DOI: 10.1007/s12017-013-8237-y

Cite this article as:
Squitti, R., Polimanti, R., Siotto, M. et al. Neuromol Med (2013) 15: 515. doi:10.1007/s12017-013-8237-y

Abstract

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.

Keywords

Alzheimer’s diseaseCopperCeruloplasminATP7BWilson’s disease

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rosanna Squitti
    • 1
    • 2
  • Renato Polimanti
    • 3
  • Mariacristina Siotto
    • 2
    • 4
  • Serena Bucossi
    • 1
    • 2
  • Mariacarla Ventriglia
    • 1
    • 2
  • Stefania Mariani
    • 1
    • 2
  • Fabrizio Vernieri
    • 2
  • Federica Scrascia
    • 2
  • Laura Trotta
    • 2
  • Paolo Maria Rossini
    • 5
    • 6
  1. 1.Department of NeuroscienceAFaR-Ospedale Fatebenefratelli HospitalRomeItaly
  2. 2.Department of Neurology“Campus Bio-Medico” UniversityRomeItaly
  3. 3.Department of Biology“Tor Vergata” UniversityRomeItaly
  4. 4.Don Carlo Gnocchi Foundation ONLUSMilanItaly
  5. 5.Department of ImagingCasa di Cura San RaffaeleCassinoItaly
  6. 6.Institute of NeurologyCatholic UniversityRomeItaly