Amyloid beta, mitochondrial dysfunction and synaptic damage: implications for cognitive decline in aging and Alzheimer's disease

Trends Mol Med. 2008 Feb;14(2):45-53. doi: 10.1016/j.molmed.2007.12.002. Epub 2008 Jan 22.


Recent studies of postmortem brains from Alzheimer's disease (AD) patients and transgenic mouse models of AD suggest that oxidative damage, induced by amyloid beta (Abeta), is associated with mitochondria early in AD progression. Abeta and amyloid-precursor protein are known to localize to mitochondrial membranes, block the transport of nuclear-encoded mitochondrial proteins to mitochondria, interact with mitochondrial proteins, disrupt the electron-transport chain, increase reactive oxygen species production, cause mitochondrial damage and prevent neurons from functioning normally. Furthermore, accumulation of Abeta at synaptic terminals might contribute to synaptic damage and cognitive decline in patients with AD. Here, we describe recent studies regarding the roles of Abeta and mitochondrial function in AD progression and particularly in synaptic damage and cognitive decline.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Cognition Disorders / metabolism*
  • Disease Progression
  • Humans
  • Mice
  • Mitochondria / metabolism*
  • Models, Biological
  • Oxidative Stress
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure


  • Amyloid beta-Peptides