Oral Treponema denticola Infection Induces Aβ1-40 and Aβ1-42 Accumulation in the Hippocampus of C57BL/6 Mice

Accumulation of amyloid-beta (A beta) in the brain is a central component of pathology in Alzheimer's disease. A growing volume of evidence demonstrates 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 A beta remain to be unclear. In this study, we demonstrated that T. denticola was able to enter the brain and act directly on nerve cells resulting in intra- and extracellular A beta(1-40) and A beta(1-42) accumulation in the hippocampus of C57BL/6 mice by selectively activating both beta-secretase and gamma-secretase. Furthermore, both KMI1303, an inhibitor of beta-secretase, as well as DAPT, an inhibitor of gamma- secretase, were found to be able to inhibit the effect of T. denticola on A beta accumulation in N2a neuronal cells. Overall, it is concluded that T. denticola increases the expression of A beta(1-42) and A beta(1-40) by its regulation on beta-site amyloid precursor protein cleaving enzyme-1 and presenilin 1.

Automated summary

The study indicates that Treponema denticola can enter the brain and directly affect nerve cells, resulting in the accumulation of A beta. Inhibitors such as KMI1303 and DAPT can suppress the effect of T. denticola on A beta.