Oral Treponema denticola infection induces Aβ1-40 and Aβ1-42 accumulation in the hippocampus of C57BL/6 mice

Abstract Accumulation of amyloid-β (Aβ) in the brain is a central component of pathology in Alzheimer’s disease. A growing number of evidences demonstrate close associations between periodontal pathogens including Porphyromonas gingivalis ( P. gingivalis ) and Treponema denticola ( T. denticola ) and AD. However, the effect and mechanisms of T. denticola on accumulation of Aβ remain to be unclear. In this study, we demonstrated that T. denticola was able to enter brain and act directly on nerve cells resulting in intra and extracellular Aβ 1−40 and Aβ 1−42 accumulation in the hippocampus of C57BL/6 mice by selectively activating both β-secretase and γ-secretase. Furthermore, both KMI1303, an inhibitor of β- secretase, as well as DAPT, an inhibitor of γ- secretase were found to be able to inhibit the effect of T. denticola on Aβ accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of Aβ 1−42 and Aβ 1−40 by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and Presenilin 1.