An Epigenetic Manifestation of Alzheimer's Disease: DNA Methylation

Abstract

Alzheimer's disease (AD), the most common form of dementia, has a complex pathogenesis. The number of AD patients has increased in recent years due to population aging, while a trend toward a younger age of onset has arisen, imposing a substantial burden on society and families, and garnering extensive attention. DNA methylation has recently been revealed to play an important role in AD onset and progression. DNA methylation is a critical mechanism regulating gene expression, and alterations in this mechanism dysregulate gene expression and disrupt important pathways, including oxidative stress responses, inflammatory reactions, and protein degradation processes, eventually resulting in disease. Studies have revealed widespread changes in AD patients' DNA methylation in the peripheral blood and brain tissues, affecting multiple signaling pathways and severely impacting neuronal cell and synaptic functions. This review summarizes the role of DNA methylation in the pathogenesis of AD, aiming to provide a theoretical basis for its early prevention and treatment.

Fig. 1.

Diagram of the mechanism that DNA methylation in Alzheimer’s disease. DNA in cells is methylated under the combined action of DNA methyltransferase (DNMT) and S-adenosyl methionine (SAM), which regulates gene expression, damages neuronal cells, and regulates immune inflammation and oxidative stress, thus leading to the occurrence of Alzheimer’s disease. SORBS3, sorbin and SH3 domain containing 3; ANK1, Ankyrin 1; RHBDF2, rhomboid 5 homolog 2; SLC2A4, solute carrier family 2A; IL-1$\beta$, interleukin 1$\beta$; IL-6, interleukin 6; TNF$\alpha$, tumor necrosis factor $\alpha$; Arc, activity regulated cytoskeleton associated protein. This image is an original image, its production software is WPS Office (12.1.0.16388, Kingsoft Corporation, Beijing, China).