The functional neurophysiology of the amyloid precursor protein (APP) processing pathway

Neuropharmacology. 2010 Sep-Oct;59(4-5):243-67. doi: 10.1016/j.neuropharm.2010.02.011. Epub 2010 Feb 16.

Abstract

Amyloid beta (Abeta) peptides derived from proteolytic cleavage of amyloid precursor protein (APP) are thought to be a pivotal toxic species in the pathogenesis of Alzheimer's disease (AD). Furthermore, evidence has been accumulating that components of APP processing pathway are involved in non-pathological normal function of the CNS. In this review we aim to cover the extensive body of research aimed at understanding how components of this pathway contribute to neurophysiological function of the CNS in health and disease. We briefly outline changes to clinical neurophysiology seen in AD patients before discussing functional changes in mouse models of AD which range from changes to basal synaptic transmission and synaptic plasticity through to abnormal synchronous network activity. We then describe the various neurophysiological actions that are produced by application of exogenous Abeta in various forms, and finally discuss a number or other neurophysiological aspects of the APP pathway, including functional activities of components of secretase complexes other than Abeta production.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology*
  • Amyloid beta-Protein Precursor / metabolism
  • Amyloid beta-Protein Precursor / physiology*
  • Animals
  • Humans
  • Neural Pathways / metabolism
  • Neural Pathways / pathology
  • Neuronal Plasticity / physiology
  • Signal Transduction / physiology*
  • Synapses / metabolism
  • Synapses / pathology

Substances

  • Amyloid beta-Protein Precursor