【Background】 Brain amyloid beta (Abeta) is accumulated from 20 years before Alzheimer's disease (AD) onset, and microglia is implicated in promoting AD pathogenesis. LPS from P. gingivalis (PgLPS), the periodontal bacteria, is detected in AD brain. 【Aim】 In this study, we test our hypothesis that PgLPS enhances microglia-mediated neuroinflammtion in Abeta exposure environment.【Methods & Results】 MG6 microglial cells were exposed to PgLPS (0.1 ug/mL), Abeta_1-42 (Abeta, 0.1uM) or co-exposed to Abeta (0.1 uM) and PgLPS (0.1 ug/mL). Inflammatory mediators and NFkB signaling were examined. In comparison to control MG6 cells, mRNA expressions of TNF-α, IL-1beta and IL-6 were induced from 1 h after exposure to PgLPS but not Abeta. Interestingly, mRNA expressions of TNF-α, IL-1beta and IL-6 were significantly increased in Abeta and PgLPS co-exposed (AL) MG6 cells from 3 h in compassion to those in PgLPS-exposed cells. TNF-α production were significantly elevated in AL-exposed MG6 cells from 3 h in compassion to that in PgLPS-exposed ones. Furthermore, phosphorylation of IκB and nuclear translocation of p65 NF-κB were up-regulated in PgLPS-exposed MG6 cells but not that in Abeta-exposed cells. Phosphorylation of IκB and nuclear translocation of p65 NF-κB were significantly up-regulated in AL-exposed MG6 cells in compassion to that in PgLPS-exposed cells. 【Conclusion】 The observations strongly suggest that PgLPS enhances microglia-related neuroinflammtion in Abeta exposure environment. The present study provides a new mechanism of periodontitis involving in the early pathologies of AD.