Background:Alzheimer’s disease (AD) and bone loss are clinically exacerbated. However, the mechanism of exacerbation remains understood. Objective:We tested our hypothesis that periodontitis is involved in the exacerbation, contributing to AD pathologies. Methods:The bone, memory, and inflammationin bone and brain were examined in 12-month-old mice after systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (P gLPS) for 3 consecutive weeks. Results:Compared with control mice, bone loss in tibia (26% decrease) and memory decline (47% decrease) were induced in mice with a positive correlation after exposure to P gLPS (r = 0.7378, p = 0.0011). The IL-6 and IL-17 expression in tibia was negatively correlated with the bone volume/total tissue volume (r = –0.6619, p = 0.0052; r = –0.7129, p = 0.0019), while that in the cortex was negatively correlated with the memory test latency (r = –0.7198, p = 0.0017; p = 0.0351, r = –0.5291). Furthermore, the IL-17 expression in microglia was positively correlated with Aβ 42 accumulation in neurons (r = 0.8635, p < 0.0001). In cultured MG6 microglia, the P gLPS-increased IL-6 expression was inhibited by a PI3K-specific inhibitor (68% decrease), and that of IL-17 was inhibited by IL-6 antibody (41% decrease). In cultured N2a neurons, conditioned medium from P gLPS-stimulated microglia (MCM) but not P gLPS increased the productions of AβPP, CatB, and Aβ 42, which were significantly inhibited by pre-treatment with IL-17 antibody (67%, 51%, and 41% decrease). Conclusion:These findings demonstrated that chronic systemic exposure to P gLPS simultaneously induces inflammation-dependent bone loss and AD-like pathologies by elevating IL-6 and IL-17 from middle age, suggesting that periodontal bacteria induce exacerbation of bone loss and memory decline, resulting in AD progression.

中文翻译：

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全身暴露于牙龈卟啉单胞菌的脂多糖会导致中年小鼠骨质流失相关的阿尔茨海默病样病理。

背景：阿尔茨海默病 (AD) 和骨质流失在临床上会加重。然而，恶化的机制仍然被理解。目的：我们检验了我们的假设，即牙周炎与恶化有关，导致 AD 病理。方法：对12个月大的小鼠全身暴露于牙龈卟啉单胞菌脂多糖（P gLPS）连续3周后，检查其骨骼、记忆和骨骼和大脑炎症。结果：与对照小鼠相比，暴露于 P gLPS 后，小鼠胫骨骨质流失（减少 26%）和记忆力下降（减少 47%）呈正相关（r = 0.7378，p = 0.0011）。胫骨中 IL-6 和 IL-17 的表达与骨体积/总组织体积呈负相关（r = –0.6619，p = 0.0052；r = –0.7129，p = 0.0019），而皮层中的与记忆测试延迟呈负相关（r = –0.7198，p = 0.0017；p = 0.0351，r = –0.5291）。此外，小胶质细胞中 IL-17 的表达与神经元中 Aβ 42 的积累呈正相关（r = 0.8635，p < 0.0001）。在培养的 MG6 小胶质细胞中，P gLPS 增加的 IL-6 表达被 PI3K 特异性抑制剂抑制（减少 68%），IL-17 的表达被 IL-6 抗体抑制（减少 41%）。在培养的 N2a 神经元中，来自 P gLPS 刺激的小胶质细胞 (MCM) 而不是 P gLPS 的条件培养基增加了 AβPP、CatB 和 Aβ 42 的产生，这些被 IL-17 抗体预处理显着抑制 (67%, 51 %，减少 41%）。结论：