阿尔茨海默病（AD）是以进行性认知障碍为表现的神经退行性疾病，已成为老年医学面临的最严峻问题。AD感染致病理论被“重新发现”，成为新热点。牙周炎是由菌斑生物膜引起的慢性感染性疾病，其最主要致病菌牙龈卟啉单胞菌及其毒力因子脂多糖（P.g-LPS）在AD患者脑内被发现，提示牙周炎和AD互相关联。信号传导和转录激活因子3（STAT3）是脑内疾病普遍存在的信号级联分子，它多靶点参与AD病理进程。前期发现牙周炎模型鼠学习记忆下降，STAT3被激活，神经炎症，Aβ增多；给STAT3抑制剂可逆转。本研究拟用牙周炎模型、Stat3条件敲除鼠，从行为、神经电生理和细胞共培养等系统研究P.g-LPS对STAT3介导的小胶质细胞-和神经元互作的影响及机制，以期阐明P.g-LPS激活脑内STAT3信号通路，调控神经元胶质细胞-神经元互作是造成认知障碍的重要机制，即加深AD病理生理机制理解，还为AD预防提供潜在新靶点。

Alzheimer's Diseases (AD) is one of the most deleterious neurodegenerative diseases. In our aging society, it has become one of the most disastrous plagues of modern humanity. Clinical trials targeting Aβ in the brain have mostly failed. It is in urgent need of the new hypotheses in order to explain AD pathogenesis and explore new targets for intervention to prevent and treat the disease. Many years ago, the “infection hypothesis” was proposed, but it received little attention. Recently, the “infection hypothesis” has been “rediscovered”.. Periodontitis is a chronic infectious disease caused by dental plaque biofilm, which leads to the damage of periodontal support tissues. As numerous epidemiological associations link CP to multiple systemic conditions, it is paid much attention to periodontal medicine. Porphyromonas gingivalis DNA and LPS, the most important virulence of periodontitis, were detected in AD patients, indicating the relationship between periodontitis and AD. However, studies still lack sufficient experimental evidence. Signal transducers and activators of transcription 3 (STAT3) is a transcription factor that is activated in response to cytokines, intercellular mediators, and growth factors. It could be involved in the progress of AD. In our previous study, Porphyromonas gingivalis LPS-induced peridontitis model was used to investigate the association between periodontitis and AD-like cognitive dysfunction. Learning and memory of mice declined. Neuroinflammation and STAT3 signal pathway were activated, which could be reversed by the STAT3 inhibitor. . In present study, both periodontitis model and STAT3 conditional knockout model will be used to systematically study the effects of STAT3 signaling on microglia-neuron interaction by Porphyromonas gingivalis-derived LPS. Neuroethology, histopathology, electrophysiology and cell co-culture will be used. Our research aims to clarify whether Porphyromonas gingivalis LPS could induce STAT3 signal pathway in brain and regulate microglia-neuron interactions, which is an important mechanism for cognitive dysfunction. This study will further deepen the understanding of the pathophysiological mechanism of AD as well as exploring a potential new target for the prevention and treatment of AD..