DNA Methylation in Alzheimer's Disease

Abstract

To date, DNA methylation is the best characterized epigenetic modification in Alzheimer's disease. Involving the addition of a methyl group to the fifth carbon of the cytosine pyrimidine base, DNA methylation is generally thought to be associated with the silencing of gene expression. It has been hypothesized that epigenetics may mediate the interaction between genes and the environment in the manifestation of Alzheimer's disease, and therefore studies investigating DNA methylation could elucidate novel disease mechanisms. This chapter comprehensively reviews epigenomic studies, undertaken in human brain tissue and purified brain cell types, focusing on global methylation levels, candidate genes, epigenome wide approaches, and recent meta-analyses. We discuss key differentially methylated genes and pathways that have been highlighted to date, with a discussion on how new technologies and the integration of multiomic data may further advance the field.

Keywords: Alzheimer’s disease; Brain cell types; Brain tissue; DNA methylation; Epigenetics.