口腔卡他莫拉菌在阿尔茨海默病发病机制中的作用研究

微生物炎症反应假说是目前阿尔茨海默病（Alzheimer’s disease, AD）研究领域的热点，而AD患者口腔菌群特点以及是否参与疾病发生尚不明确。我们前期发现AD患者口腔中莫拉克斯氏菌属水平显著升高，推测其可能与AD发病相关。为验证此假设，我们在部分AD患者脑脊液中检测到该菌属中最常见的菌种—卡他莫拉菌；同时发现其外膜蛋白UspA1可影响Aβ表达水平；另外，AD遗传学研究还发现表达人UspA1受体蛋白的基因CEACAM1是AD易感基因，基于此，我们推测卡他莫拉菌可能通过CEACAM1介导UspA1参与AD发病。因此，本课题拟首先明确卡他莫拉菌能否经口腔进入脑组织；其次明确卡他莫拉菌及UspA1对AD病理改变的影响；最后明确卡他莫拉菌通过UspA1-CEACAM1-Aβ通路参与AD疾病发生。本研究旨在揭示卡他莫拉菌在AD发病中的作用及机制，从而为开发AD治疗药物提供新思路和理论依据。

Currently, the hypothesis of microbial inflammatory response is a hot topic in the research field of pathogenesis Alzheimer’s disease (AD), however, it is unknown that the bacteria distribution lied in oral cavity in AD patients, as well as whether it is involved in the occurrence of AD. In our previous work, we found that the Moraxella was significantly increased in oral cavity in AD patients. Moreover, the most common species in Moraxella genus, Moraxella catarrhalis, was identified in cerebrospinal fluid in several AD patients. Besides, Moraxella catarrhalis can secrete UspA1 protein affecting Aβ levels in our vitro study. Combined with our recent finding in AD genetics research that CEACAM1, expressing UspA1 receptor protein, may be an AD susceptibility gene, we speculate that CEACAM1 protein may mediate UspA1 to affect AD pathological changes. Based on the above findings, our study intends to first clarify whether Moraxella catarrhalis in the oral cavity can enter the central nervous system; secondly, clarify the effect of Moraxella catarrhalis and UspA1 on pathological changes of AD; thirdly, clarify that Moraxella catarrhalis is involved in the development of AD through the UspA1-CEACAM1-Aβ pathway. We believe that our study can reveal the role and mechanism of oral Moraxella catarrhalis in the pathogenesis of AD, and provide new ideas and theoretical basis for the development of AD treatment drugs.