阿尔茨海默病(AD)是老年期最常见的痴呆类型，其中95%病例为散发性AD。研究证实炎性衰老是散发性AD的重要病理机制，然而其调节途径及分子机制尚未阐明，迄今缺乏有效的防治手段。近年来，老龄化过程菌-肠-脑轴失衡在神经退行性疾病（NDDs）中的作用得到重视。新近研究显示，肠道菌群紊乱激活的模式识别受体信号通路在NDDs的菌-肠-脑轴免疫途径中发挥重要作用。ALPK1是2018年发现的新型模式识别受体。我们前期研究发现，ALPK1受体激活与散发性AD模型小鼠的菌-肠-脑轴失衡及炎性衰老密切相关。本研究拟应用ALPK1基因敲除小鼠、伪无菌小鼠及散发性AD小鼠的粪菌移植模型，进一步研究ALPK1信号通路在老年期菌-肠-脑轴失衡介导的炎性衰老及认知功能减退中的调节作用及机制，以期为探讨散发性AD炎性发病机制及潜在的干预靶标提供新的思路。

Alzheimer's disease is the most common type of dementia in the elderly, among which sporadic AD accounts for about 95% of the total AD cases. Studies have demonstrated that inflammaging is an important pathological mechanism of sporadic AD, but the regulatory pathway and underlying molecular mechanism have not yet been elucidated. Up to date, there is no effective approach for the prevention and treatment of AD. In recent years, the role of the microbiota-gut-brain axis imbalance in neurodegenerative diseases (NDDs) gets attention. The latest research suggests that the signaling pathway activation of pattern recognition receptor (PRR) plays a key role in the immune route of the microbiota-gut-brain axis in NDDs. ALPK1 is a novel PRR identified first in 2018. Our previous study found that ALPK1 activation was associated with the microbiota-gut-brain axis imbalance and inflammaging in sporadic AD mice. This project is to further investigate the regulatory effects and underlying mechanisms of ALPK1 signaling pathway in aged microbiota-gut-brain axis imbalance induced inflammaging and cognitive decline by using ALPK1 knockout mice, pseudoaseptic mice and fecal bacteria transplanted mice of sporadic AD model. This study is expected to provide the new lines of thinking for the inflammatory pathogenesis and the potential intervention targets of sporadic AD.