Epigenetic regulation in the pathophysiology of Alzheimer's disease.
Chouliaras L., Rutten BP., Kenis G., Peerbooms O., Visser PJ., Verhey F., van Os J., Steinbusch HW., van den Hove DL.
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.