Alzheimer病（AD）是以进行性认知功能障碍为特征的中枢神经系统退行性疾病，目前尚无有效手段阻断其进程。APP在细胞器之间的转运过程已成为干预Aβ代谢的新靶点，但其具体过程及调控因素未明。早期研究及我们的预实验结果表明，细胞膜蛋白CD147在线粒体内质网相关膜结构（MAM）中，对局部APP的代谢及转运过程具有重要的调节作用，但其具体的分子机制还有待深入探讨。为此我们提出假说：细胞浆连接蛋白Hook1可能通过内化作用使CD147进入早期内体，然后CD147通过kiss and run这种方式进入线粒体。最终，线粒体通过与内质网的桥接使CD147具有调节局部γ分泌酶活性的作用，从而代谢局部的APP。为验证这一假说，我们将通过分子生物学方法干预上述过程中的关键蛋白，并在CD147基因敲除动物模型及上述关键蛋白的病毒干预模型中对其进行验证，为阻断AD的进程提供新的思路。

Alzheimer disease (AD) is a neurodegenerative disease of the central nervous system characterized by progressive cognitive dysfunction. APP transport between organelles has become a new target of intervention of Aβmetabolism, but the specific process and regulatory factors is still unknown. Early research and our experimental results indicate that CD147 located in the mitochondria associated endoplasmic reticulum (MAM) membrane may play an important role in the metabolism and transport process of local APP. But its precise molecular mechanism remains to be explored. To this end, we put forward the hypothesis that Hook1, a cytosolic binding protein, may internalize CD147 into the early endosomes. Then CD147 may enter mitochondria out membrane through kiss and run process between endosomes and mitochondria. In the end, by tethering endoplasmic reticulum, mitochondria CD147 might be able to regulate the activity of local gamma secretase located in MAM, and finally help to metabolize local APP. To test this hypothesis, we will intervene the key proteins of the aforementioned process by molecular biological methods, CD147 heterozygous gene knockout in animal models. This would provide new insight for blocking the progress of AD.