Abstract
Objective: This review summarizes recent findings on the epigenetics of Alzheimer's disease (AD) and provides therapeutic strategies for AD.Methods: We searched the following keywords: “genetics,” “epigenetics,” “Alzheimer's disease,” “DNA methylation,” “DNA hydroxymethylation,” “histone modifications,” “non-coding RNAs,” and “therapeutic strategies” in PubMed.Results: In this review, we summarizes recent studies of epigenetics in AD, including DNA methylation/hydroxymethylation, histone modifications, and non-coding RNAs. There are no consistent results of global DNA methylation/hydroxymethylation in AD. Epigenetic genome-wide association studies show that many differentially methylated sites exist in AD. Several studies investigate the role of histone modifications in AD; for example, histone acetylation decreases, whereas H3 phosphorylation increases significantly in AD. In addition, non-coding RNAs, such as microRNA-16 and BACE1-antisense transcript (BACE1-AS), are associated with the pathology of AD. These epigenetic changes provide us with novel insights into the pathogenesis of AD and may be potential therapeutic strategies for AD.Conclusion: Epigenetics is associated with the pathogenesis of AD, including DNA methylation/hydroxymethylation, histone modifications, and non-coding RNAs, which provide potential therapeutic strategies for AD.
Highlights
Alzheimer’s disease (AD) is a devastating neurological disease characterized by progressive cognitive impairments
For apolipoprotein E gene (APOE), two studies show that there is no significant difference in DNA methylation levels in postmortem brain tissues between AD patients and normal controls [39, 40]
Watson et al identify 479 differentially methylated regions in patients with AD compared to normal controls by performing a genome-wide screen of DNA methylation in the temporal gyrus of AD, and 475 of these regions are involved in neuron function and development [67]
Summary
We summarizes recent studies of epigenetics in AD, including DNA methylation/hydroxymethylation, histone modifications, and non-coding RNAs. There are no consistent results of global DNA methylation/hydroxymethylation in AD. Epigenetic genome-wide association studies show that many differentially methylated sites exist in AD. Several studies investigate the role of histone modifications in AD; for example, histone acetylation decreases, whereas H3 phosphorylation increases significantly in AD. Non-coding RNAs, such as microRNA-16 and BACE1-antisense transcript (BACE1-AS), are associated with the pathology of AD.
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