Department of Neuroscience, AFaR - Fatebenefratelli Hospital "San Giovanni Calibita", Rome, Italy Laboratory of Neurodegeneration, IRCSS San Raffaele Pisana, Rome, Italy.
J Alzheimers Dis. 2014;38(4):809-22. doi: 10.3233/JAD-131247.
The fraction of copper not bound to ceruloplasmin seems altered in Alzheimer's disease (AD). We have addressed this notion evaluating all the studies carried out from 1996 until March 2013 by means of meta-analysis. We performed our analysis on diverse indices evaluating the relationship between copper and ceruloplasmin in general circulation, namely 'Non-Cp copper', '% Non-Cp copper', and 'Adjusted copper'. For Non-Cp copper and % Non-Cp copper, the correct stoichiometry between copper and ceruloplasmin (6-8 atoms of copper for each ceruloplasmin molecule) in healthy controls has been adopted as criterion for the study to be included in the meta-analysis evaluating data with the canonic Walshe's formula for Non-Cp copper. Copper to ceruloplasmin ratio (Cu:Cp), which is an internal quality control check for ceruloplasmin calibration, was used as an index of the actual stoichiometry in the specimens. Adjusted (Adj-Cp) copper, even though less reliable, was calculated, allowing the evaluation of all the studies selected. An additional meta-analysis of systemic total copper was re-calculated accounting for all the studies carried out from 1983 to March 2013. Ten studies were analyzed in the meta-analysis for Non-Cp copper and % Non-Cp copper reaching a pooled total of 599 AD subjects and 867 controls. For Adj-Cp copper, 14 studies were analyzed with a pooled total of 879 AD and 1,712 controls. 27 studies were considered for systemic total copper meta-analysis, with a pooled total of 1,393 AD and 2,159 controls. All the copper indices analyzed were significantly higher in AD subjects compared to healthy controls.
在阿尔茨海默病（AD）中，与铜蓝蛋白结合的铜比例似乎发生了改变。我们通过荟萃分析评估了 1996 年至 2013 年 3 月期间进行的所有研究，以解决这一问题。我们使用了不同的指标来评估铜在整个循环系统中与铜蓝蛋白的关系，即“非-Cp 铜”、“%非-Cp 铜”和“调整后的铜”。对于非-Cp 铜和%非-Cp 铜，我们采用健康对照者中铜与铜蓝蛋白的正确化学计量比（每个铜蓝蛋白分子有 6-8 个铜原子）作为纳入荟萃分析的标准，用于评估使用非-Cp 铜的 Walshe 经典公式的数据。铜与铜蓝蛋白的比值（Cu:Cp）是铜蓝蛋白校准的内部质量控制检查指标，用于评估标本的实际化学计量比。即使不太可靠，我们也计算了调整后的（Adj-Cp）铜，从而可以评估所有选定的研究。我们还重新计算了从 1983 年至 2013 年 3 月期间进行的所有研究的系统性总铜的额外荟萃分析。我们对非-Cp 铜和%非-Cp 铜进行了 10 项荟萃分析，共纳入 599 名 AD 患者和 867 名对照者。对于 Adj-Cp 铜，我们对 14 项研究进行了荟萃分析，共纳入 879 名 AD 患者和 1712 名对照者。我们对 27 项系统性总铜荟萃分析进行了考虑，共纳入 1393 名 AD 患者和 2159 名对照者。与健康对照者相比，所有分析的铜指标在 AD 患者中均显著升高。
