School for Mental Health and Neuroscience (MHeNS), Faculty of Health, Medicine and Life Sciences, European Graduate School of Neuroscience (EURON), Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht, The Netherlands.
Prog Neurobiol. 2010 Apr;90(4):498-510. doi: 10.1016/j.pneurobio.2010.01.002. Epub 2010 Jan 25.
With the aging of the population, the growing incidence and prevalence of Alzheimer's disease (AD) increases the burden on individuals and society as a whole. To date, the pathophysiology of AD is not yet fully understood. Recent studies have suggested that epigenetic mechanisms may play a pivotal role in its course and development. The most frequently studied epigenetic mechanisms are DNA methylation and histone modifications, and investigations relevant to aging and AD are presented in this review. Various studies on human postmortem brain samples and peripheral leukocytes, as well as transgenic animal models and cell culture studies relevant to AD will be discussed. From those, it is clear that aging and AD are associated with epigenetic dysregulation at various levels. Moreover, data on e.g. twin studies in AD support the notion that epigenetic mechanisms mediate the risk for AD. Conversely, it is still not fully clear whether the observed epigenetic changes actually represent a cause or a consequence of the disease. This is mainly due to the fact that most clinical investigations on epigenetics in AD are conducted in samples of patients already in an advanced stage of the disease. Evidently, more research is needed in order to clarify the exact role of epigenetic regulation in the course and development of AD. Research on earlier stages of the disease could provide more insight into its underlying pathophysiology, possibly contributing to the establishment of early diagnosis and the development of more effective treatment strategies.
随着人口老龄化，阿尔茨海默病（AD）的发病率和患病率不断增加，给个人和整个社会带来了沉重的负担。迄今为止，AD 的病理生理学尚未完全阐明。最近的研究表明，表观遗传机制可能在其发生和发展中起着关键作用。最常研究的表观遗传机制是 DNA 甲基化和组蛋白修饰，本综述介绍了与衰老和 AD 相关的研究。讨论了各种关于人类死后脑组织样本和外周血白细胞的研究，以及与 AD 相关的转基因动物模型和细胞培养研究。从这些研究中可以清楚地看出，衰老和 AD 与各种水平的表观遗传失调有关。此外，关于 AD 的双胞胎研究等数据支持这样一种观点，即表观遗传机制介导 AD 的风险。相反，目前尚不完全清楚观察到的表观遗传变化实际上是疾病的原因还是结果。这主要是因为大多数 AD 表观遗传学的临床研究都是在疾病晚期患者的样本中进行的。显然，需要进行更多的研究，以阐明表观遗传调控在 AD 发生和发展中的确切作用。对疾病早期阶段的研究可以更深入地了解其潜在的病理生理学，可能有助于建立早期诊断和开发更有效的治疗策略。
