Leptomeningeal cells play an important role in preventing brain from the peripheral virulence factors. Porphyromonas gingivalis (P.g) is the main pathogenic bacteria of periodontitis and reported involved in the linkage of systemic inflammation and Alzheimer's disease. However, the molecular mechanism underlines the transduce effect from peripheral to central nervous system of leptomeningeal cells are still not clear. In this study, we aimed to elucidate the effects of leptomeningeal cells in neurodegeneration after exposure to P.g using cultured cells. The pro-inflammatory mediators in leptomeningeal cells were significantly increased after exposure to P.g from 1h to 12h. Exposure to P.g (MOI=10) for 3h significantly increased the expression of pro-IL-1β, mIL-1β and secretion of IL-1β. The Aβ processing genes in neurons were significantly increase following the culture with LCM for 24h. These observations suggested that leptomeningeal cells may induce the neurodegeneration after exposure to P.g thus providing a bridge between peripheral infection and neuronal neurodegeneration in Alzheimer's disease.