Zhang Weiwei, Jiao Bin, Zhou Miaojin, Zhou Tao, Shen Lu
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Stem Cells Int. 2016;2016:7828049. doi: 10.1155/2016/7828049. Epub 2016 May 24.
Alzheimer's disease (AD) is the most prevalent type of dementia and its pathology is characterized by deposition of extracellular β-amyloid plaques, intracellular neurofibrillary tangles, and extensive neuron loss. While only a few familial AD cases are due to mutations in three causative genes (APP, PSEN1, and PSEN2), the ultimate cause behind the rest of the cases, called sporadic AD, remains unknown. Current animal and cellular models of human AD, which are based on the Aβ and tau hypotheses only, partially resemble the familial AD. As a result, there is a pressing need for the development of new models providing insights into the pathological mechanisms of AD and for the discovery of ways to treat or delay the onset of the disease. Recent preclinical research suggests that stem cells can be used to model AD. Indeed, human induced pluripotent stem cells can be differentiated into disease-relevant cell types that recapitulate the unique genome of a sporadic AD patient or family member. In this review, we will first summarize the current research findings on the genetic and pathological mechanisms of AD. We will then highlight the existing induced pluripotent stem cell models of AD and, lastly, discuss the potential clinical applications in this field.
阿尔茨海默病（AD）是最常见的痴呆类型，其病理学特征为细胞外β淀粉样蛋白斑块沉积、细胞内神经原纤维缠结以及广泛的神经元丢失。虽然只有少数家族性AD病例是由三个致病基因（APP、PSEN1和PSEN2）的突变引起的，但其余病例（称为散发性AD）背后的最终病因仍不清楚。目前基于Aβ和tau假说的人类AD动物和细胞模型仅部分类似于家族性AD。因此，迫切需要开发新的模型以深入了解AD的病理机制，并发现治疗或延缓疾病发作的方法。最近的临床前研究表明，干细胞可用于模拟AD。事实上，人类诱导多能干细胞可以分化为与疾病相关的细胞类型，这些细胞类型概括了散发性AD患者或家庭成员的独特基因组。在这篇综述中，我们将首先总结目前关于AD遗传和病理机制的研究结果。然后，我们将重点介绍现有的AD诱导多能干细胞模型，最后讨论该领域的潜在临床应用。
