申请者前期蛋白组学研究发现转基因AD鼠脑内多种蛋白与AD病人血清中的改变一致，它们在血清中的表达水平与认知能力（MMSE）密切相关。提示这些蛋白是潜在的AD早期诊断、评价疗效的生物标志物。本项目拟进一步开展AD药物新靶点，新模型及AD相关机理研究。主要内容包括：1. 药物蛋白组学研究，AD转基因动物在药物治疗后的蛋白表达谱的改变，找出对药物治疗敏感，与AD病理改变相关的蛋白；2. 在多种AD动物模型上验证，已发现的标志物及药物敏感蛋白的表达，以确定与AD病人更为接近的痴呆动物模型；3. 关键蛋白或生物标志物的表达、调控研究，探讨AD发病机理及这些蛋白作为药物靶点的可能性。拟解决关键问题：寻找新的人—动物模型一体化的抗AD药物新靶点，及药效评价新指标，建立新型AD药物评价模型并阐明某些AD发病机理。

Our preliminary proteomic studies have found that a variety of multiple proteins in the brain of transgenic AD mouse were consistent with that in serum of AD patients. These proteins expressions in serum were closely related the cognitive ability (MMSE), suggesting that these proteins might be the potential biomarkers for AD early diagnosis and therapeutic evaluation. Based on this, the present project is planned to further develop the new drug targets and the new models for AD, and AD-related mechanism. The main contents include: 1).Observe the protein expression profiles after drug treatment in AD transgenic mouse by proteomic study, and found the proteins sensitive to drug treatment and associated with AD pathology. 2). Identify the above proteins in a variety of animal models of AD, such AD transgenic mouse, aging mouse and cholinergic nerve damaged model. We wish to find an animal model much close to AD patients. 3). Investigate the regulation and expression of key proteins or biomarkers. To investigate AD pathogenesis and the possibilities of these proteins as drug targets. Key issues: to find the indices of integration of AD patients and animal models in preclinical drug evaluation, and AD animal model which is strong correlated with the clinic.