title: Copper dysfunction in Alzheimer's disease: from meta-analysis of biochemical studies to new insight into genetics.
abstract: The involvement of body copper metabolism in the development of Alzheimer's disease (AD) - the most common form of dementia - is a deeply investigated issue in recent years. Copper is essential for life, but in excess it can be toxic. Recently, it has been hypothesized that copper toxicity may be a contributory factor in the etiology of the neurodegenerative disease AD. Studies on copper evaluation in AD vs. healthy controls collected in the latest 30 years and merged in a meta-analysis demonstrate that serum copper is slightly increased in AD. A specific form of copper, the copper non-bound to ceruloplasmin, or 'free' copper, seems to best characterize this increase in copper in AD patients. Clinical studies from us and other groups have demonstrated that free copper is associated with the typical deficits of AD, incipient AD and mild cognitive impairment, and specific cerebrospinal markers. Moreover, very recent data addressing molecular processes underlying copper dysfunction in AD have indicated that genetic variations of K832R and R952K Single Nucleotide Polymorphisms (SNPs) of the Wilson's disease gene ATP7B are associated also with sporadic AD. Specifically, ATP7B encodes for the protein ATPase 7B which controls free copper status in the body, and both R allele in K832R and K allele in R952K ATP7B SNPs are associated with an increased risk of having AD. Even though copper dysfunction cannot be assumed as a determinant of the disease, its causative, rather than associated, role in AD pathology as risk factor can be claimed.
authors.affiliation: Department of Neuroscience, AFaR - Osp. Fatebenefratelli, Rome, Italy. rosanna.squitti@afar.it
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D006527:Hepatolenticular Degeneration / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015201:Meta-Analysis as Topic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases