Activation of microglial cells by beta-amyloid protein and interferon-gamma

Nature. 1995 Apr 13;374(6523):647-50. doi: 10.1038/374647a0.


Alzheimer's disease is the most common cause of progressive intellectual failure. The lesions that develop, called senile plaques, are extracellular deposits principally composed of insoluble aggregates of beta-amyloid protein (A beta), infiltrated by reactive microglia and astrocytes. Although A beta, and a portion of it, the fragment 25-35 (A beta (25-35)), have been shown to exert a direct toxic effect on neurons, the role of microglia in such neuronal injury remains unclear. Here we report a synergistic effect between A beta and interferon-gamma (IFN-gamma) in triggering the production of reactive nitrogen intermediates and tumour-necrosis factor-alpha (TNF-alpha) from microglia. Furthermore, using co-culture experiments, we show that activation of microglia with IFN-gamma and A beta leads to neuronal cell injury in vitro. These findings suggest that A beta and IFN-gamma activate microglia to produce reactive nitrogen intermediates and TNF-alpha, and this may have a role in the pathogenesis of neuronal degeneration observed in ageing and Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism
  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Cells, Cultured
  • Inflammation Mediators / metabolism
  • Interferon-gamma / metabolism*
  • Mice
  • Molecular Sequence Data
  • Nerve Degeneration
  • Neuroglia / metabolism*
  • Nitrogen / metabolism
  • Peptide Fragments / metabolism
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism


  • Amyloid beta-Peptides
  • Inflammation Mediators
  • Peptide Fragments
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Nitrogen