Epigenetic mechanisms in Alzheimer's disease.

The worldwide increase in life expectancy is leading to an increase in age-dependent diseases, including nonfamilial, sporadic Alzheimer's disease (AD), which is the subject of this review. The etiology and pathophysiology of the disease is not fully understood, but present observations suggest that, in addition to genetic risk factors, environmental influences may be involved via epigenetic mechanisms. Currently, there is no effective treatment, but there are indications that lifestyle has an impact on the development of the disease. This view is supported by preclinical studies not only showing that human lifestyle-equivalent interventions have a positive effect on cognitive function in animal models of AD, but also indicating the involvement of underlying epigenetic mechanisms. After a brief overview of the most characteristic chromatin modifications, ie, DNA methylation and histone modifications, epigenetic changes associated with aging are considered, given that aging is the most important risk factor for AD. This is followed by a description of some epigenetic alterations recognized in AD. The impact of environmental factors and lifestyle on the epigenome is then considered. Epigenetic treatments with HDAC inhibitors and RNA-based drugs are considered, which - while still in preclinical stages - are promising for potential benefit. It is concluded that while awaiting results from clinical trials in progress, focusing on lifestyle adjustments with an epigenetic background are the best way to prevent/delay the onset of this devastating disease.