Possible Involvement of Small Oligomers of Amyloid-β Peptides in 15-Deoxy-Δ12,14 Prostaglandin J2-Sensitive Microglial Activation

Abstract

In Alzheimer’s disease, fibrillar amyloid-β (Aβ) peptides form senile plaques associated with microglia. However, the relationship between Aβ peptides and microglia is not fully understood. In this study, the incubation of Aβ1-40 (Aβ40) produced small oligomers, while incubation with Aβ1-42 (Aβ42) caused large molecular aggregates. Microglial production of nitrite, interleukin-6 and tumor necrosis factor-α was induced by Aβ40, but not Aβ42. This production was significantly reduced by 15-deoxy-Δ12,14 prostaglandin J2, and it was completely suppressed by β-sheet breaker peptide, Leu-Pro-Phe-Phe-Asp. These results suggest that small oligomers, rather than large molecular aggregates, mediate microglial activation induced by Aβ peptides.