The societal burden presented by Alzheimer’s disease warrants both innovative and expedient means by which its underlying molecular causes can be both identified and mechanistically exploited to discern novel therapeutic targets and strategies. The conserved characteristics, defined neuroanatomy, and advanced technological application of Caenorhabditis elegans render this metazoan an unmatched tool for probing neurotoxic factors. In addition, its short lifespan and importance in the field of aging make it an ideal organism for modeling age-related neurodegenerative disease. As such, this nematode system has demonstrated its value in predicting functional modifiers of human neurodegenerative disorders. Here, we review how C. elegans has been utilized to model Alzheimer’s disease. Specifically, we present how the causative neurotoxic peptides, amyloid-β and tau, contribute to disease-like neurodegeneration in C. elegans and how they translate to human disease. Furthermore, we describe how a variety of transgenic animal strains, each with distinct utility, have been used to identify both genetic and pharmacological modifiers of toxicity in C. elegans. As technological advances improve the prospects for intervention, the rapidity, unparalleled accuracy, and scale that C. elegans offers researchers for defining functional modifiers of neurodegeneration should speed the discovery of improved therapies for Alzheimer’s disease.

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秀丽隐杆线虫对阿尔茨海默氏病的遗传和药理发现

由阿尔茨海默氏病引起的社会负担需要既新颖又方便的手段，通过它既可以识别其潜在的分子原因，又可以机械地利用它来辨别新的治疗靶点和策略。秀丽隐杆线虫的保守特性，明确的神经解剖学和先进的技术应用使该后生动物成为探测神经毒性因子的无与伦比的工具。此外，它的寿命短并且在衰老领域中很重要，使其成为模拟与年龄有关的神经退行性疾病的理想生物。这样，该线虫系统已证明其在预测人类神经退行性疾病的功能调节剂中的价值。在这里，我们回顾一下秀丽隐杆线虫已用于模拟阿尔茨海默氏病。具体而言，我们介绍了致病性神经毒性肽淀粉样蛋白β和tau如何导致秀丽隐杆线虫的疾病样神经变性以及它们如何转化为人类疾病。此外，我们描述了如何使用各种具有不同用途的转基因动物品系来鉴定秀丽隐杆线虫毒性的遗传和药理修饰剂。随着技术的进步改善了干预的前景，秀丽隐杆线虫为研究人员定义神经退行性功能调节剂提供的快速性，无与伦比的准确性和规模将加快发现阿尔茨海默氏病改良疗法的速度。