阿尔茨海默病（AD）是一种进行性发展的神经退行性疾病，严重影响患者的生存质量。随着人口老龄化加剧，患病人数日益增加，治愈AD迫在眉睫。AD脑中小胶质细胞高表达CD22，对淀粉样蛋白（Aβ）吞噬清除作用减弱，敲除CD22可逆转其吞噬清除作用。同时老化的小胶质细胞表现为异常活化状态，产生大量免疫炎症因子，申请者前期研究发现AD模型鼠脑中多种补体成分呈高度表达，造成神经元损伤。本项目利用具有抗补体活性的绿原酸构建金属有机框架（Zn-CA）用于负载CD22 shRNA及Aβ核酸适配体，同时利用铁蛋白修饰的红细胞膜囊泡进行伪装，用于AD的诊断及免疫调控治疗。本研究通过探讨CD22在小胶质细胞吞噬清除中的作用及绿原酸对补体成分C1q/C4a/C4b/C3a等的活性影响，阐明纳米药物系统增强小胶质细胞对Aβ的清除及抑制补体过度活化引起免疫损伤的机制，为AD提供新的治疗靶点及安全有效的诊疗一体化平台。

Alzheimer's disease (AD) is a progressive neurodegenerative disease that seriously affects the quality of life of patients. As the aging of population intensifies, the number of AD patients are increasing. The cure for AD isextremely urgent. CD22 was overexpressed in microglial cells of AD brain, which weakens the phagocytosis and clearance of amyloid (Aβ). Knockout of CD22 can reverse its phagocytosis and clearance. At the same time, aging microglia were abnormally activated and produced a large number of immune inflammatory factors. Previous research by the applicant found that various complement components in the brain of AD mice were highly expressed, causing neuronal damage. This project uses chlorogenic acid with anti-complement activity to construct a metal-organic framework (Zn-CA) for loading CD22 shRNA and Aβ aptamers, and uses ferritin modified RBC membrane vesicles to camouflage for the diagnosis and immunomodulatory therapy of AD. This study will explore the role of CD22 in phagocytosis and clearance of microglia and the effect of chlorogenic acid on complement components C1q/C4a/C4b/C3a, and elucidate the mechanism by which the nano-drug system enhances the clearance of microglia cells and inhibits the immune damage caused by the over-activation of complement, which will provide new therapeutic targets and a safe and effective theranostics platform for AD.