Epigenetic Mechanisms in Alzheimer's Disease

M.      Daniilidou; M.      Koutroumani; M.      Tsolaki

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative disorders affecting elderly people (over 65 years old). Only a small percentage (less than 5%) of the disease is consistent with the Mendelian form of inheritance. The rest, named as Late Onset Alzheimer's Disease (more than 95%), is characterized as a complex multi-factorial disorder, missing familial traits. Although some genes have been implicated in the pathogenesis and the risk of developing sporadic AD, they only account for the minority of LOAD cases. Thus, over the past few years emerging data suggest a potential role of epigenetic mechanisms and chromatin remodeling on neurodegenerative processes leading to dementia. Alterations on the epigenomic machinery cause aberrant DNA methylation and histone acetylation. Therefore, these changes trigger alterations on the transcrpiptional level of genes involved in the pathogenesis of AD, such as APP. In this review we summarize recent advances on synaptic dysfunction and cognitive decline caused by common epigenetic modifications. We also discuss potential treatment strategies targeting on the epigenetic machinery.

Keywords: Alzheimer's disease, epigenetics, DNA methylation, histone acetylation, neurodegenerative, Mendelian form of inheritance, multi-factorial disorder, epigenetic machinery