Recent studies have shown that oligomeric amyloid-β (oAβ) peptide can 
potentially activate microglia in addition to inducing more potent neurotoxicity 
compared with fibrillar Aβ (fAβ); however, its mechanisms of action remain 
unclear. This study was designed to investigate the possible mechanisms involved 
in the microglial activation induced by oAβ in BV-2 microglial cells. The 
results showed that oAβ induced activated properties of microglia, including 
higher proliferative capacity as well as increased production of reactive oxygen 
species, nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1β 
(IL-1β). NADPH oxidase inhibitors [diphenylene iodonium (DPI) and apocynin 
(4-hydroxy-3-methoxy-acetophenone)] prevented the microglial activation induced 
by oAβ, suggesting that NADPH oxidase activation was involved in microglial 
activation. In addition, TNF-α and IL-1β, which are massively released by 
activated microglia, significantly induced the activation of microglia, thereby 
resulting in the production of NO and proliferation of microglia, respectively. 
These effects could be inhibited by diphenylene iodonium and apocynin, 
indicating a self-cycle regulated by NADPH oxidase in microglial activation in 
response to oAβ. In conclusion, microglial activation induced by oAβ is possibly 
mediated by NADPH oxidase, suggesting that oAβ, which is normally considered a 
neurotoxin, may also lead to indirect neuronal damage through the 
pro-inflammation activation of microglia in Alzheimer's disease and that NADPH 
oxidase could be a potential target to prevent oAβ-induced inflammatory 
neurodegeneration.