Department of Neurobiology and Behavior, University of California Irvine, Irvine, California 92697-4545, USA.
Stem Cells. 2012 Dec;30(12):2612-8. doi: 10.1002/stem.1240.
Alzheimer's disease (AD) is the leading cause of age-related dementia, affecting over 5 million people in the U.S. alone. AD patients suffer from progressive neurodegeneration that gradually impairs their memory, ability to learn, and carry out daily activities. Unfortunately, current therapies for AD are largely palliative and several promising drug candidates have failed in recent clinical trials. There is therefore an urgent need to improve our understanding of AD pathogenesis, create innovative and predictive models, and develop new and effective therapies. In this review, we will discuss the potential of stem cells to aid in these challenging endeavors. Because of the widespread nature of AD pathology, cell-replacement strategies have been viewed as an incredibly challenging and unlikely treatment approach. Yet recent work shows that transplantation of neural stem cells (NSCs) can improve cognition, reduce neuronal loss, and enhance synaptic plasticity in animal models of AD. Interestingly, the mechanisms that mediate these effects appear to involve neuroprotection and trophic support rather than neuronal replacement. Stem cells may also offer a powerful new approach to model and study AD. Patient-derived induced pluripotent stem cells, for example, may help to advance our understanding of disease mechanisms. Likewise, studies of human embryonic and NSCs are helping to decipher the normal functions of AD-related genes; revealing intriguing roles in neural development.
阿尔茨海默病（AD）是与年龄相关的痴呆症的主要原因，仅在美国就影响了超过 500 万人。AD 患者遭受进行性神经退行性变，逐渐损害他们的记忆、学习能力和进行日常活动的能力。不幸的是，目前用于 AD 的治疗方法主要是姑息性的，最近的临床试验中几种有前途的候选药物都失败了。因此，迫切需要提高我们对 AD 发病机制的理解，创建创新和预测性模型，并开发新的有效治疗方法。在这篇综述中，我们将讨论干细胞在这些具有挑战性的努力中的潜力。由于 AD 病理学的广泛性质，细胞替代策略被视为一种极具挑战性且不太可能的治疗方法。然而，最近的工作表明，神经干细胞（NSC）的移植可以改善认知，减少 AD 动物模型中的神经元损失，并增强突触可塑性。有趣的是，介导这些效应的机制似乎涉及神经保护和营养支持，而不是神经元替代。干细胞也可能为 AD 的模型和研究提供一种强大的新方法。例如，患者来源的诱导多能干细胞可能有助于我们加深对疾病机制的理解。同样，对人类胚胎和 NSCs 的研究有助于破译 AD 相关基因的正常功能；揭示了在神经发育中引人入胜的作用。
