阿尔茨海默病(AD)是最常见的一种老年性痴呆，脑内老年斑的形成是其重要的病理学特征，其机制尚未完全明了。研究显示通过改变肠道微生物能够改善老年认知功能和减少老年斑的生成。PET/MR技术同时具有PET和MR的优势，能够从分子影像学角度观察大脑功能变化，是研究活体大脑变化的最佳工具。本课题科学假说是，肠道微生物通过改变体内IL-33水平，影响老年斑的生成。本项目利用PET/MR技术有助于从分子影像角度精确定量分析肠道微生物对AD老年斑的效应。项目组在前期研究基础上，通过临床试验确定AD组和健康对照组的致病菌和益生菌，培养并移植到APP/PS1双转基因AD模型小鼠中，观察这些致病菌和益生菌对模型小鼠老年斑形成的效应及其机制。本结果将为AD的临床治疗提供新途径，为进一步阐明肠道微生物参与AD发病机制提供基础资料。

Alzheimer's disease (AD) is the most common dementia, its pathologic hallmark is the formation of senile plaque, in which β-amyloid peptide (Aβ) is a major component, and its mechanism has still not completely been unreveiled. Studies revealed that alteration of gut microbiota could alter cognitive function and reduce the formation of senile plaques in aging individuals, but little understanding on the mechanism of regulating cognitive function of AD via gut microbiota is also unknown. PET/MR is an ideal molecular technology to study brain variation in animal model and patients in vivo. Based on our previous results, our hypothesis is that gut microbiota may modulate the formation of Aβ in brain by changing interleukin (IL)-33. Therefore, this study will include studies on AD patients and APP/PS1 double transgenic mouse. We will get the potential pathogenic bacteria and probiotic bacteria, which are easily cultivated in vitro, from AD patients and healthy controls, and cultivate those bacteria and transplant them into APP/PS1 double transgenic mice. Then, to assess the effect of those pathogenic and probiotic bacteria on the formation of senial plaque via utilizing PET/MR. Meanwhile, IL-33 level in surum and brain will be checked in APP/PS1 mice. The results will offer a new target and new way of treating AD, and provide the base and envidence for further clarifying the mechanism of gut microbiota in pathogenesis of AD.