Increased susceptibility to Aβ toxicity in neuronal cultures derived from familial Alzheimer's disease (PSEN1-A246E) induced pluripotent stem cells
Increased susceptibility to Aβ toxicity in neuronal cultures derived from familial Alzheimer's disease (PSEN1-A246E) induced pluripotent stem cells
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DOI：
10.1016/j.neulet.2016.12.060
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发表时间：
2017-02-03
影响因子：
2.5
通讯作者：
Soto, Claudio
中科院分区：
文献类型：
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作者：
Armijo, Enrique;Gonzalez, Cesar;Soto, Claudio
阿尔茨海默病(AD)是老年痴呆最常见的原因，也是全球主要的死亡原因之一。诱导多能干细胞(IPSC)的产生促进了患者体细胞干细胞的产生和分化，为体外模拟AD和其他疾病提供了新的机会。在这项研究中，我们从健康个体以及散发性(SAD)和家族性AD(FAD，PSEN1-A246E突变)患者的皮肤成纤维细胞中获得了IPSCs。将IPSC分化为神经元前体细胞(IPSC-NPC)，并对其进行淀粉样β蛋白(Aβ)毒性试验。我们发现，与来自健康和悲伤个体的神经元相比，来自FAD患者的神经元对Aβ1-42寡聚体的敏感性更高。我们的发现表明，PSEN1-A246E突变患者的神经元具有内在特性，使它们更容易受到AD大脑中Aβ1-42寡聚体的毒性影响。(C)2017爱思唯尔爱尔兰有限公司。保留所有权利。
Alzheimer's disease (AD) is the most common cause of late-life dementia and represents one of the leading causes of death worldwide. The generation of induced pluripotent stem cells (iPSC) has facilitated the production and differentiation of stem cells from patients somatic cells, offering new opportunities to model AD and other diseases in vitro. In this study, we generated iPSCs from skin fibroblasts obtained from a healthy individual, as well as sporadic (sAD) and familial AD (fAD, PSEN1-A246E mutation) patients. iPSC lines were differentiated into neuronal precursors (iPSC-NPCs) and neurons that were subjected to amyloid beta (A beta) toxicity assays. We found that neurons derived from the fAD patient have a higher susceptibility to A beta 1-42 oligomers compared with neurons coming from healthy and sAD individuals. Our findings suggest that neurons from patients with PSEN1-A246E mutation have intrinsic properties that make them more susceptible to the toxic effects of A beta 1-42 oligomers in the AD brain. (C) 2017 Elsevier Ireland Ltd. All rights reserved.