Dashinimaev Erdem B, Artyuhov Alexander S, Bolshakov Alexey P, Vorotelyak Ekaterina A, Vasiliev Andrey V
Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.
Pirogov Russian National Research Medical University, Moscow, Russia.
J Alzheimers Dis. 2017;56(2):835-847. doi: 10.3233/JAD-160945.
People with Down syndrome (DS) are at high risk of developing pathology similar to Alzheimer's disease (AD). Modeling of this pathology in vitro may be useful for studying this phenomenon. In this study, we analyzed three different cultures of neural cells carrying trisomy of chromosome 21, which were generated by directed differentiation from induced pluripotent stem cells (iPS cells). We report here that in vitro generated DS neural cells have abnormal metabolism of amyloid-β (Aβ) manifested by increased secretion and accumulation of Aβ granules of Aβ42 pathological isoform with upregulated expression of the APP gene. Additionally, we found increased expression levels of genes that are considered to be associated with AD (BACE2, RCAN1, ETS2, TMED10), as compared to healthy controls. Thus, the neural cells generated from induced pluripotent stem cells with DS reproduce initial cellular signs of AD-type pathology and can be useful tools for modeling and studying this variant of AD in vitro.
唐氏综合征（DS）患者患与阿尔茨海默病（AD）相似病理的风险很高。在体外对这种病理进行建模可能有助于研究这一现象。在本研究中，我们分析了三种不同的携带21号染色体三体的神经细胞培养物，这些细胞是由诱导多能干细胞（iPS细胞）定向分化产生的。我们在此报告，体外产生的DS神经细胞具有异常的淀粉样β蛋白（Aβ）代谢，表现为Aβ42病理异构体的Aβ颗粒分泌增加和积累，同时APP基因表达上调。此外，与健康对照相比，我们发现被认为与AD相关的基因（BACE2、RCAN1、ETS2、TMED10）表达水平升高。因此，由DS诱导多能干细胞产生的神经细胞重现了AD型病理的初始细胞迹象，可成为体外建模和研究这种AD变体的有用工具。
