Synaptic Dysfunction in Alzheimer's Disease: Aβ, Tau, and Epigenetic Alterations

Mol Neurobiol. 2018 Apr;55(4):3021-3032. doi: 10.1007/s12035-017-0533-3. Epub 2017 Apr 29.

Abstract

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized in the early stages by loss of learning and memory. However, the mechanism underlying these symptoms remains unclear. The best correlation between cognitive decline and pathological changes is in synaptic dysfunction. Histopathological hallmarks of AD are the abnormal aggregation of Aβ and Tau. Evidence suggests that Aβ and Tau oligomers contribute to synaptic loss in AD. Recently, direct links between epigenetic alterations, such as dysfunction in non-coding RNAs (ncRNAs), and synaptic pathologies have emerged, raising interest in exploring the potential roles of ncRNAs in the synaptic deficits in AD. In this paper, we summarize the potential roles of Aβ, Tau, and epigenetic alterations (especially by ncRNAs) in the synaptic dysfunction of AD and discuss the novel findings in this area.

Keywords: Alzheimer’s disease; Epigenetic alterations; Synaptic dysfunction; Tau; miRNA.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Epigenesis, Genetic*
  • Humans
  • Models, Biological
  • Synapses / pathology*
  • tau Proteins / metabolism*

Substances

  • Amyloid beta-Peptides
  • tau Proteins