海马神经网络退变是导致阿尔茨海默氏病（AD）患者认知功能障碍的重要原因。保护海马神经元新生（AHN）可以有效预防和改善AD早期的认知功能障碍，但AHN在AD发病前就已经开始出现障碍，其发生机制尚不清楚。Tau蛋白在经历依赖性AHN的调节、及AD的发生和发展过程中均发挥着关键作用。我们的前期研究结果提示，tau蛋白在海马齿状回dlx5/6阳性中间神经元内的聚集可能是引起AD早期局部神经网络去抑制，并导致AHN障碍的重要原因。本项目拟在前期研究工作的基础上，利用细胞/分子生物学、选择性基因操控、蛋白组/磷酸化蛋白组学分析等技术手段，在微环路水平，进一步探讨齿状回dlx5/6阳性中间神经元tau聚集引起AHN障碍的分子机制，并寻找相应的药物干预靶点。研究结果将从保护神经新生的角度，为AD的早期预防和治疗提供分子靶标。

Hippocampal network degeneration contributes to learning and memory deficits in Alzheimer's disease (AD). Promoting adult hippocampal neurogenesis (AHN) benefits the prevention and amelioration of cognitive impairments at the early stage of AD. However, AHN is impaired before the onset of AD, and the underlying mechanisms remain to be elucidated. Tau protein play crucial roles both in the regulation of experience-dependent neurogenesis and in the onset or development of AD. Our primary results indicated that tau accumulation in dentate gyrus dlx5/6-positive interneurons induced local neural network deinhibition and contributed to the AHN impairment in AD. In the present study, we will investigate molecular mechanisms underlying how tau accumulation in dlx5/6-positive interneurons impairs AHN, to find novel targets for AHN preservation for AD prevention or treatment at early stages.