[Background and purpose] Cerebral amyloid angiopathy (CAA) is observed in more than 80% of Alzheimer’s disease (AD) patients. Receptor for advanced glycation end products (RAGE) mediates amyloid β (Aβ) influx into brain. In this study, we test our hypothesis that P.g promotes Aβ influx. [Methods and Results] In hCMEC/D3 cells, RAGE expression was significantly increased in the P.g-infected hCMEC/D3 cells in compassion to that in uninfected cells. The P.g-increased RAGE expression in hCMEC/D3 cells was inhibited by pretreating with NFκB inhibitor. In addition, cathepsin B (CatB) was increased in the P.g-infected hCMEC/D3 cells, and CatB specific inhibitor suppressed both IκBα degradation and RAGE expression in the P.g-infected hCMEC/D3 cells. Using fluorescently labeled Aβ1-42, the amount of Aβ1-42 in basolateral medium of the P.g-infected hCMEC/D3 cells was 16-fold higher than that in uninfected cells. In 15-month old mice, RAGE expression in CD31-positive cerebral endothelial cells was increased 2-fold in the P.g-infected mice in compassion to that in PBS-injected mice. Furthermore, Aβ1-42 expression which surrounding the CD31-positive cerebral endothelial cells was increased 11-fold in in compassion to that in PBS-injected mice. Moreover, the memory function was decreased in the P.g-infected mice. [Conclusion] These observations demonstrate that up-regulated RAGE expression in cerebral endothelial cells mediates the Aβ influx after P. gingivalis infection, and CatB plays a critical role in regulating the NF-κB/RAGE expression.
