Siotto Mariacristina, Simonelli Ilaria, Pasqualetti Patrizio, Mariani Stefania, Caprara Deborah, Bucossi Serena, Ventriglia Mariacarla, Molinario Rossana, Antenucci Mirca, Rongioletti Mauro, Rossini Paolo Maria, Squitti Rosanna
Don Carlo Gnocchi Foundation ONLUS, Milan, Italy.
Fatebenefratelli Foundation for Health Research and Education, AFaR Division, Rome, Italy.
J Alzheimers Dis. 2016;50(4):1181-9. doi: 10.3233/JAD-150611.
Meta-analyses demonstrate copper involvement in Alzheimer's disease (AD), and the systemic ceruloplasmin status in relation to copper is an emerging issue. To deepen this matter, we evaluated levels of ceruloplasmin concentration, ceruloplasmin activity, ceruloplasmin specific activity (eCp/iCp), copper, non-ceruloplasmin copper iron, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype in a sample of 84 AD patients and 58 healthy volunteers. From the univariate logistic analyses we found that ceruloplasmin concentration, eCp/iCp, copper, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype were significantly associated with the probability of AD. In the multivariable logistic regression analysis, we selected the best subset of biological predictors by the forward stepwise procedure. The analysis showed a decrease of the risk of having AD for eCp/iCp (p = 0.001) and an increase of this risk for non-ceruloplasmin copper (p = 0.008), age (p = 0.001), and APOE-ɛ4 allele (p < 0.001). The estimated model showed a good power in discriminating AD patients from healthy controls (area under curve: 88% ; sensitivity: 66% ; specificity 93%). These data strength the breakdown of copper homeostasis and propose eCp/iCp as a reliable marker of ceruloplasmin status.
荟萃分析表明铜与阿尔茨海默病（AD）有关，而与铜相关的系统性铜蓝蛋白状态是一个新出现的问题。为了深入研究这个问题，我们评估了84例AD患者和58名健康志愿者样本中的铜蓝蛋白浓度、铜蓝蛋白活性、铜蓝蛋白比活性（eCp/iCp）、铜、非铜蓝蛋白结合铜、铁、转铁蛋白、铜蓝蛋白/转铁蛋白比值以及APOE基因型。单因素逻辑分析发现，铜蓝蛋白浓度、eCp/iCp、铜、转铁蛋白、铜蓝蛋白/转铁蛋白比值以及APOE基因型与AD发病概率显著相关。在多变量逻辑回归分析中，我们通过向前逐步法选择了最佳的生物学预测指标子集。分析显示，eCp/iCp降低患AD的风险（p = 0.001），而非铜蓝蛋白结合铜（p = 0.008）、年龄（p = 0.001）和APOE-ɛ4等位基因（p < 0.001）则增加患AD的风险。估计模型在区分AD患者和健康对照方面具有良好的效能（曲线下面积：88%；敏感性：66%；特异性：93%）。这些数据强化了铜稳态的破坏，并提出eCp/iCp作为铜蓝蛋白状态的可靠标志物。
