Activation of microglial cells by beta-amyloid protein and interferon-gamma.
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.
Meda
L
L
Institute of General Pathology, University of Verona, Italy.
Cassatella
M A
MA
Szendrei
G I
GI
Otvos
L
L
Baron
P
P
Villalba
M
M
Ferrari
D
D
Rossi
F
F
D000375:Aging / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009410:Nerve Degeneration; D009457:Neuroglia / Q000378:metabolism*; D009584:Nitrogen / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018836:Inflammation Mediators; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D009584:Nitrogen