阿尔茨海默(AD)疾病的致病机理尚未明确，目前针对单一因素的药物失败率较高，因此多因素协同作用的治疗策略有待进一步深入研究。申请人前期工作发现，磷脂纳米盘(ApoA-I-ND)是理想的药物递送载体。由于ApoA-I蛋白对AD相关的Aß及tau蛋白具有特异性结合；同时抗氧化酶对AD早期神经损伤起重要保护作用。因此本项目拟采用磷脂纳米盘作为AD多靶向载体，协同含硒酶的抗氧化作用，制备含硒磷脂纳米盘(Se-ND)，研究其穿越血脑屏障靶向结合Aß及tau蛋白机制、抗氧化酶学性质、对细胞氧化应激指标及AD相关指标的影响，初步探索Se-ND对小鼠认知能力的影响。本项目将在分子、细胞及动物水平探讨针对AD的多因素协同作用机制，为发展AD早期多靶点及抗氧化损伤协同防御的治疗策略奠定基础，同时有望为AD早期的预防和干预治疗提供新的思路。

AD is an age-related, progressive and irreversible neurodegenerative disease. The pathogenic mechanism is not clear, and effective drugs and therapies are still lacking. At present, single targets drug make relatively high failure risk. Therefore, further study focus on multi-targets strategy. In the previous research, the applicant found that ApoA-I Nanodisc (ApoA-I-ND) is an efficient drug delivery carrier, with high binding ability to Aß amyloid and tau protein ,which is the pathological features of AD; And antioxidant enzymes play an important protective role in early AD neurological damage. This project plans to utilize ApoA-I-ND as a multi-targeting carrier, with antioxidant effect, exploring the mechanism of synergy against AD at the molecular, cellular, and animal levels. Based on the previous work, we plan to construct a selenium-containing ApoA-I nanodisc (Se-ND) to study the binding mechanism between ApoA-I-ND / Se-ND and Aß / tau proteins, and also the inhibit aggregation mechanism; Test the antioxidant properties of Se-ND; In the response of AD to cellular oxidative stress, we plan to clarify the effect of Se-ND on AD-related indicators; Utilitz the AD mouse model to explore the effect of Se-ND on mouse cognition ability. This study will be useful to clarify the mechanism of Se-ND targeting Aß and tau protein across the blood-brain barrier, and to reveal the multi-targeting and anti-oxidation synergy mechanism of Se-ND in the early oxidative damage states of AD, which will provided new ideas for further AD therapeutic strategy .