Fong Sheng, Teo Emelyne, Ng Li Fang, Chen Ce-Belle, Lakshmanan Lakshmi Narayanan, Tsoi Sau Yee, Moore Philip Keith, Inoue Takao, Halliwell Barry, Gruber Jan
Internal Medicine Residency Programme, SingHealth Group, Singapore.
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore.
Sci Rep. 2016 Sep 22;6:33781. doi: 10.1038/srep33781.
Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear. Using a novel C. elegans AD strain with constitutive neuronal Aβ expression that displays neuromuscular defects and age-dependent behavioural dysfunction reminiscent of AD, we have shown that mitochondrial bioenergetic deficit is an early event in AD pathogenesis, preceding dysfunction of mitochondrial electron transfer chain (ETC) complexes and the onset of global metabolic failure. These results are consistent with an emerging view that AD may be a metabolic neurodegenerative disease, and also confirm that Aβ-driven metabolic and mitochondrial effects can be reproduced in organisms separated by large evolutionary distances.
阿尔茨海默病（AD）是一种进行性神经疾病，其特征是大脑中主要以Aβ形式存在的β淀粉样蛋白（Aβ）沉积。线粒体功能障碍和能量代谢受损是AD发病机制的重要组成部分。然而，它们与AD病理之间的因果关系和时间关系仍不清楚。利用一种新型的秀丽隐杆线虫AD品系，其具有组成型神经元Aβ表达，表现出神经肌肉缺陷和与年龄相关的行为功能障碍，类似于AD，我们已经表明线粒体生物能量缺陷是AD发病机制中的早期事件，早于线粒体电子传递链（ETC）复合物功能障碍和整体代谢衰竭的发生。这些结果与一种新出现的观点一致，即AD可能是一种代谢性神经退行性疾病，也证实了Aβ驱动的代谢和线粒体效应可以在进化距离较远的生物体中重现。
