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: Rosanna Squitti
• Journal: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (J Trace Elem Med Biol) Vol. 28 Issue 4 Pg. 482-5 (Oct 2014) ISSN: 1878-3252 [Electronic] Germany
• PMID: 25066791 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemical References

• Cation Transport Proteins
• Copper
• Ceruloplasmin
• Adenosine Triphosphatases
• ATP7B protein, human
• Copper-Transporting ATPases

Topics

• Adenosine Triphosphatases (metabolism)
• Alzheimer Disease (blood, metabolism, pathology)
• Cation Transport Proteins (metabolism)
• Ceruloplasmin (metabolism)
• Cognitive Dysfunction (blood, metabolism, pathology)
• Copper (blood)
• Copper-Transporting ATPases
• Humans