Synaptic retrogenesis and amyloid-beta in Alzheimer's disease

J Alzheimers Dis. 2009;16(1):1-14. doi: 10.3233/JAD-2009-0918.

Abstract

Pathological hallmarks of Alzheimer's disease (AD) include synaptic and neuronal degeneration and the presence of extracellular deposits of amyloid-beta (Abeta) in senile plaques in the cerebral cortex. Although these brain lesions may be seen also in aged non-demented individuals, the increase in brain Abeta is believed by many to represent the earliest event in the disease process. Accumulating evidence suggests that Abeta, which is highly conserved by evolution, may have an important physiological role in synapse elimination during brain development. An intriguing idea is that this putative function can become pathogenic if activated in the aging brain. Here, we review the literature on the possible physiological roles of Abeta and its precursor protein AbetaPP during development with special focus on electrophysiological findings.

Publication types

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

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / physiology
  • Amyloid beta-Peptides / toxicity
  • Amyloid beta-Protein Precursor / metabolism
  • Amyloid beta-Protein Precursor / physiology
  • Animals
  • Brain / growth & development
  • Cell Proliferation
  • Glutamic Acid / physiology
  • Humans
  • Long-Term Potentiation / physiology
  • Memory / physiology
  • Neuronal Plasticity / physiology
  • Synapses / pathology
  • Synapses / physiology*

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Glutamic Acid