Epigenetic Mechanisms in Memory and Cognitive Decline Associated with Aging and Alzheimer's Disease

Int J Mol Sci. 2021 Nov 13;22(22):12280. doi: 10.3390/ijms222212280.


Epigenetic mechanisms, which include DNA methylation, a variety of post-translational modifications of histone proteins (acetylation, phosphorylation, methylation, ubiquitination, sumoylation, serotonylation, dopaminylation), chromatin remodeling enzymes, and long non-coding RNAs, are robust regulators of activity-dependent changes in gene transcription. In the brain, many of these epigenetic modifications have been widely implicated in synaptic plasticity and memory formation. Dysregulation of epigenetic mechanisms has been reported in the aged brain and is associated with or contributes to memory decline across the lifespan. Furthermore, alterations in the epigenome have been reported in neurodegenerative disorders, including Alzheimer's disease. Here, we review the diverse types of epigenetic modifications and their role in activity- and learning-dependent synaptic plasticity. We then discuss how these mechanisms become dysregulated across the lifespan and contribute to memory loss with age and in Alzheimer's disease. Collectively, the evidence reviewed here strongly supports a role for diverse epigenetic mechanisms in memory formation, aging, and neurodegeneration in the brain.

Keywords: DNA; epigenetics; hippocampus; histone; memory; neurodegeneration.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Aging* / genetics
  • Aging* / metabolism
  • Alzheimer Disease* / genetics
  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / physiopathology
  • Animals
  • Brain* / metabolism
  • Brain* / physiopathology
  • Chromatin Assembly and Disassembly*
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / metabolism
  • Cognitive Dysfunction* / physiopathology
  • DNA Methylation / genetics
  • Epigenesis, Genetic*
  • Humans
  • Memory Disorders* / genetics
  • Memory Disorders* / metabolism
  • Memory Disorders* / physiopathology
  • Neuronal Plasticity / genetics
  • Protein Processing, Post-Translational / genetics