DNA methylation in the pathology of Alzheimer's disease: from gene to cognition

Ann N Y Acad Sci. 2020 Sep;1475(1):15-33. doi: 10.1111/nyas.14373. Epub 2020 Jun 3.

Abstract

Alzheimer's disease (AD) is a debilitating disorder that manifests with amyloid beta plaque deposition, neurofibrillary tangles, neuronal loss, and severe cognitive impairment. Although much effort has been made to decipher the pathogenesis of this disease, the mechanisms causing these detrimental outcomes remain obscure. Over the past few decades, neuroepigenetics has emerged as an important field that, among other things, explores how reversible modifications can change gene expression to control behavior and cognitive abilities. Among epigenetic modifications, DNA methylation requires further elucidation for the conflicting observations from AD research and its pivotal role in learning and memory. In this review, we focus on the essential components of DNA methylation, the effects of aberrant methylation on gene expressions in the amyloidogenic pathway and neurochemical processes, as well as memory epigenetics in Alzheimer's disease.

Keywords: Alzheimer's disease; DNA methylation; amyloid beta; neuroepigenetics; neuroplasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology*
  • Alzheimer Disease / physiopathology
  • Brain / pathology
  • Cognition / physiology*
  • DNA Methylation / genetics*
  • Humans
  • Models, Biological