title: Copper subtype of Alzheimer's disease (AD): meta-analyses, genetic studies and predictive value of non-ceruloplasmim copper in mild cognitive impairment conversion to full AD.
abstract: Alzheimer's disease (AD) is the most common form of dementia. A myriad of complex factors contribute to AD, promoting the deposition in plaques of amyloid-beta (Aβ), which is the main constituent of this pathognomonic sign of AD at autopsy brain inspection. Aβ toxicity is related to oxidative stress, which results in synaptic loss in specific brain areas, eventually leading to cognitive decline. Metal, and especially copper, dyshomeostasis is a key factor in these processes. Recent studies have demonstrated that the serum fraction of copper that is not bound to ceruloplasmin (Non-Cp copper, also known as 'free' or labile copper) increases in a percentage of AD patients and mild cognitive impairment (MCI) subjects; this is considered a precursor of AD. Non-Cp copper is the exchangeable fraction of low molecular weight copper in serum. It is distinguished from the copper structurally bound to the ceruloplasmin protein, a master protein of iron metabolism. Non-Cp copper levels are higher than normal reference values (range 0-1.6μmol/L) in about 50% of amnestic MCI subjects and 60% of AD patients, typifying them in a subset of AD. Meta-analyses, genetic studies and a prognostic study evaluating the predictive value of Non-Cp copper in MCI conversion to full AD demonstrate the existence of this copper phenotype of AD.
authors: Fatebenefratelli Foundation for Health Research and Education, AFaR Division, "San Giovanni Calibita" Fatebenefratelli Hospital, Rome, Italy; Laboratorio di Neurodegenerazione, IRCCS San Raffaele Pisana, Italy. Electronic address: rosanna.squitti@afar.it.
authors: Rosanna
authors: R
authors: Squitti
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000544:Alzheimer Disease / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D027682:Cation Transport Proteins / Q000378:metabolism; D002570:Ceruloplasmin / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000097:blood* / Q000378:metabolism / Q000473:pathology*; D003300:Copper / Q000097:blood*; D000073840:Copper-Transporting ATPases; D006801:Humans
chemical_list: D027682:Cation Transport Proteins; D003300:Copper; D002570:Ceruloplasmin; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: ATP7B; Alzheimer's disease; Ceruloplasmin; Copper; Non-Cp copper