Introduction: Previous reports have proposed that Periodontal disease (PDis) predisposes to Alzheimer’s disease (AD), both highly prevalent pathologies among the elderly. The bacteria Aggregatibacter actinomycetemcomitans (Aa), associated with the most aggressive forms of PDis, are classified in different serotypes with distinct virulence according to the antigenicity of their lipopolysaccharide (LPS). Methods: Here, we determined the effects of purified LPS, from serotypes a, b or c of Aa, on primary cultures of microglia or mixed hippocampal cells. Results: We found that both culture types exhibited higher levels of inflammatory cytokines (IL-1β, IL-6 and TNFα) when treated with serotype b-LPS, compared with controls, as quantified by qPCR and/or ELISA. Also, cultures treated with serotype a-LPS displayed increased mRNA levels of the modulatory cytokines IL-4 and IL-10. Mixed hippocampal cultures treated with serotype b-LPS exhibited severe neuronal morphological changes and displayed increased levels of secreted Aβ_1-42 peptide. These results indicate that LPS from different Aa serotypes triggers discriminatory immune responses, which differentially affect primary hippocampal cells. Conclusion: Altogether, our results show that treatment with serotype b-LPS triggers the secretion of proinflammatory cytokines by microglia, induces neurite shrinking, and increases the extracellular Aβ1-42 levels, all features strongly associated with the etiology of AD.

简介：先前的报告提出牙周病（PDis）易患阿尔茨海默氏病（AD），这两种疾病在老年人中都非常普遍。细菌 Aggregatibacter放线杆菌 （了Aa）中，用PDIS的最积极的形式有关，根据它们的脂多糖（LPS）的抗原性的归类与独特的毒力不同的血清型。方法： 在这里，我们确定了Aa血清型a，b或c的纯化LPS 对小胶质细胞或混合海马细胞原代培养的影响。 结果： 我们发现，用血清型b-LPS处理时，与对照相比，两种培养物均表现出较高水平的炎症细胞因子（IL-1β，IL-6和TNFα），如通过qPCR和/或ELISA定量。而且，用血清型α-LPS处理的培养物显示出调节性细胞因子IL-4和IL-10的mRNA水平升高。用血清型b-LPS处理的混合海马培养物表现出严重的神经元形态变化，并分泌的_Aβ1-42 肽水平升高。这些结果表明，来自不同Aa 血清型的LPS 会触发歧视性免疫反应，从而有区别地影响原代海马细胞。 结论： 总之，我们的结果表明，用血清型b-LPS治疗可触发小胶质细胞分泌促炎细胞因子，诱导神经突缩小，并增加细胞外Aβ1-42水平，所有这些特征均与AD的病因密切相关。