Investigation of annexin A5 as a biomarker for Alzheimer's disease using neuronal cell culture and mouse model
Investigation of annexin A5 as a biomarker for Alzheimer's disease using neuronal cell culture and mouse model
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DOI：
10.1002/jnr.22427
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发表时间：
2010-09
影响因子：
4.2
通讯作者：
Mami Yamaguchi;Y. Kokai;S. Imai;K. Utsumi;Kyoichi Matsumoto;Hirohito Honda;Y. Mizue;M. Momma
中科院分区：
文献类型：
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作者：
Mami Yamaguchi;Y. Kokai;S. Imai;K. Utsumi;Kyoichi Matsumoto;Hirohito Honda;Y. Mizue;M. Momma
阿尔茨海默病（AD）与其他形式的痴呆的不同之处在于其与淀粉样β肽（Aβ）的关系。Aβ是淀粉样前体蛋白（APP）的蛋白水解产物，对神经元细胞具有毒性作用，其作用涉及细胞内Ca 2+稳态的紊乱。这种效应意味着，在神经元细胞中的蛋白质表达的变化与钙应激应提供这种疾病的分子标志物。在本研究中，我们使用与或不与Aβ孵育后的神经元细胞培养物上清液，并分离出Ca2+依赖性酸性磷脂结合组分，以进行蛋白质组学研究。在与Aβ孵育后鉴定出几种独特的蛋白质。在这些蛋白质中，我们专注于膜联蛋白A5，因为它结合可能参与钙稳态的Ca2+和脂质。Tg2576转基因小鼠（AD模型）过度表达突变型人APP显示大脑皮层中膜联蛋白A5的显著增加，但在其他器官中，包括肝、肾、肺和肠中没有。在人血浆样品中，与对照组相比，AD患者的比例中膜联蛋白A5的水平显著增加（在逻辑回归分析中P < 0.0001）。根据血浆膜联蛋白A5浓度的受试者工作特征（ROC）曲线，平均曲线下面积（AUC 0.898）表明膜联蛋白A5是AD的有利标志物。© 2010 Wiley利斯公司
Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid β peptide (Aβ). Aβ, a proteolytic product of amyloid precursor proteins (APP), has a toxic effect on neuronal cells, which involves perturbation of their Ca2+ homeostasis. This effect implies that changes of protein expression in neuronal cells with calcium stress should provide a molecular marker for this disease. In the present study, we used the supernatant from a neuronal cell culture after incubation with or without Aβ and isolated a Ca2+‐dependent acidic phospholipid binding fraction to perform a proteomic study. Several unique proteins were identified after incubation with Aβ. We focused on annexin A5, among these proteins, because it binds both Ca2+ and lipids likely to be involved in calcium homeostasis. Tg2576 transgenic mice (AD model) overexpressing mutant human APP showed a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. In human plasma samples, the level of annexin A5 was significantly increased in a proportion of AD patients compared with a control group (P < 0.0001 in the logistic regression analysis). From the receiver operating characteristic (ROC) curve with plasma annexin A5 concentrations, the mean area under the curve (AUC 0.898) suggests that annexin A5 is a favorable marker for AD. © 2010 Wiley‐Liss, Inc.