Shirotani Keiro, Matsuo Kazuya, Ohtsuki Sumio, Masuda Takeshi, Asai Masashi, Kutoku Yumiko, Ohsawa Yutaka, Sunada Yoshihide, Kondo Takayuki, Inoue Haruhisa, Iwata Nobuhisa
Department of Genome-based Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
Unit for Dementia Research and Drug Discovery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521, Japan.
J Biochem. 2017 Dec 1;162(6):391-394. doi: 10.1093/jb/mvx058.
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.
我们开发了一种简化且灵敏的方法,通过对来自阿尔茨海默病(AD)患者诱导多能干细胞(iPSC)分化的神经元的培养基进行定量靶向蛋白质组分析(液相色谱串联质谱与多重多反应监测/选择反应监测分析相结合),来鉴定AD生物标志物候选物。我们发现,α-1-酸性糖蛋白(ORM1)在AD-iPSC衍生神经元的培养基中减少,这与之前对AD患者脑脊液的观察结果一致,从而验证了我们的新策略。此外,我们的方法适用于使用患者来源的iPSC来鉴定其他神经退行性疾病的生物标志物候选物。