A simplified and sensitive method to identify Alzheimer's disease biomarker candidates using patient-derived induced pluripotent stem cells (iPSCs)

A simplified and sensitive method to identify Alzheimer's disease biomarker candidates using patient-derived induced pluripotent stem cells (iPSCs)
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使用患者来源的诱导多能干细胞 (iPSC) 识别阿尔茨海默氏病候选生物标志物的简化且灵敏的方法

DOI:
10.1093/jb/mvx058
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发表时间:
2017
影响因子:
2.7
通讯作者:
Iwata N
Iwata N
中科院分区:
生物学4区
文献类型:
--
作者:
Shirotani K;Matsuo K;Ohtsuki S;Masuda T;Asai M;Kutoku Y;Ohsawa Y;Sunada Y;Kondo T;Inoue H;Iwata N

文献摘要

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我们开发了一种简单而灵敏的方法,通过对AD患者诱导的多潜能干细胞(IPSCs)分化的神经元培养上清液进行定量和有针对性的蛋白质组学分析(结合高效液相色谱-串联质谱仪和多重多反应监测/选择性反应监测分析)来识别阿尔茨海默病(AD)生物标志物候选。我们发现AD-IPSC来源神经元的培养液中α-1-酸性糖蛋白(ORM1)减少,这与先前对AD患者脑脊液的观察一致,从而验证了我们的新策略。此外,我们的方法也适用于使用患者来源的IPSCs识别其他神经退行性疾病的生物标记物候选。
We developed a simplified and sensitive method to identify Alzheimer’s disease (AD) biomarker candidates by a quantitative and targeted proteomic analysis (combination of liquid chromatography tandem mass spectrometry and multiplexed-multiple reaction monitoring/selected reaction monitoring analysis) of culture media from neurons differentiated from induced pluripotent stem cells (iPSCs) established from AD patients. We found that alpha-1-acid glycoprotein (ORM1) was decreased in the culture media of AD-iPSC–derived neurons, consistent with previous observations for AD patient cerebrospinal fluid, thus validating our new strategy. Moreover, our method is applicable for identifying biomarker candidates for other neurodegenerative disorders using patient-derived iPSCs.