| First Author | Meda L | Year | 1995 |
| Journal | Nature | Volume | 374 |
| Issue | 6523 | Pages | 647-50 |
| PubMed ID | 7715705 | Mgi Jnum | J:274855 |
| Mgi Id | MGI:6305053 | Doi | 10.1038/374647a0 |
| Citation | Meda L, et al. (1995) Activation of microglial cells by beta-amyloid protein and interferon-gamma. Nature 374(6523):647-50 |
| abstractText | 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. |
