Soluble amyloid precursor protein 770 is a novel biomarker candidate for acute coronary syndrome
Soluble amyloid precursor protein 770 is a novel biomarker candidate for acute coronary syndrome
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DOI：
10.1002/prca.201200135
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发表时间：
2013-10
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影响因子：
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通讯作者：
S. Kitazume;A. Yoshihisa;T. Yamaki;M. Oikawa;Y. Tachida;Kazuko Ogawa;R. Imamaki;Y. Takeishi;N. Yamamoto;N. Taniguchi
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文献类型：
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作者：
S. Kitazume;A. Yoshihisa;T. Yamaki;M. Oikawa;Y. Tachida;Kazuko Ogawa;R. Imamaki;Y. Takeishi;N. Yamamoto;N. Taniguchi
大多数阿尔茨海默病患者显示血管以及脑实质中淀粉样β（Aβ）肽的沉积。我们先前发现血管内皮细胞表达淀粉样β前体蛋白（APP）770，这是一种与神经元APP 695不同的APP亚型，并且它们产生淀粉样β肽。我们分析了APP 770的糖基化，发现O-糖基化的sAPP 770优先被蛋白酶加工以产生Aβ。由于可溶性APP裂解产物sAPP被认为是阿尔茨海默病诊断的可能标志物，因此由这些变体的混合物组成的sAPP已被广泛测量。我们假设，在患者中分别测量内皮细胞APP 770裂解产物和神经元APP 695裂解产物将使我们能够区分内皮功能障碍和神经功能障碍。我们最近的研究结果显示，血浆sAPP 770水平在急性冠状动脉综合征患者中显著升高，提高了sAPP 770可能是内皮功能障碍的指标的可能性。本文就sAPP 770的表达、糖基化和加工等方面进行综述，并探讨sAPP 770作为急性冠脉综合征新的生物标志物的可能性。
Most Alzheimer disease patients show deposition of amyloid β (Aβ) peptide in blood vessels as well as the brain parenchyma. We previously found that vascular endothelial cells express amyloid β precursor protein (APP) 770, a different APP isoform from neuronal APP695, and that they produce amyloid β peptide. We analyzed the glycosylation of APP770 and found that O‐glycosylated sAPP770 is preferentially processed by proteases for Aβ production. Because the soluble APP cleavage product sAPP is considered to be a possible marker for Alzheimer disease diagnosis, sAPP, consisting of a mixture of these variants, has been widely measured. We hypothesized that measurement of the endothelial APP770 cleavage product in patients separately from that of neuronal APP695 would enable us to discriminate between endothelial and neurological dysfunctions. Our recent findings, showing that the level of plasma sAPP770 is significantly higher in patients with acute coronary syndrome, raise the possibility that sAPP770 could be an indicator of endothelial dysfunction. In this review, we first describe the expression, glycosylation, and processing of APP770, and then discuss sAPP770 as a novel biomarker candidate of acute coronary syndrome.