Accumulation of amyloid-β (Aβ) 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 Aβ 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 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.

大脑中淀粉样蛋白-β (Aβ) 的积累是阿尔茨海默病病理学的核心组成部分。越来越多的证据表明牙周病原体包括牙龈卟啉单胞菌( P. gingivalis ) 和齿状密螺旋体( T. denticola ) 与 AD之间存在密切关联。然而，T. denticola对 Aβ 积累的影响和机制尚不清楚。在这项研究中，我们证明T. denticola能够进入大脑并直接作用于神经细胞，导致细胞内和细胞外 Aβ _1-40和 Aβ _1-42通过选择性激活 β-分泌酶和 γ-分泌酶，在 C57BL/6 小鼠的海马体中积累。此外，发现 KMI1303（β-分泌酶抑制剂）和 DAPT（γ-分泌酶抑制剂）都能够抑制T. denticola对 N2a 神经元细胞中 Aβ 积累的影响。总的来说，可以得出结论，T. denticola通过调节 β 位淀粉样前体蛋白裂解酶 1 和早老素 1来增加 Aβ _1-42和 Aβ _1-40的表达。