PPP2R5C蛋白是本课题组在家族性阿尔茨海默病（AD）患者及症状前患者血浆神经元来源外泌体（NDEs）中筛选到与病程进展呈明显负相关的新的AD潜在生物标记物，并在随后散发AD患者中得到验证，提示NDEs中该蛋白表达下调可能作为AD发生的早期事件参与其发病过程。PPP2R5C是磷酸酯酶2A（PP2A）的调节亚基，后者是调节tau蛋白去磷酸化的重要磷酸酶。我们推测PPP2R5C可能作为关键调节亚基介导PP2A靶向调控tau蛋白去磷酸化而促发AD。本课题拟在此基础上，在细胞水平研究NEDs中PPP2R5C对神经元维持tau蛋白功能、微管结构及神经元活性等的影响；明确该蛋白调控tau蛋白去磷酸化及神经元凋亡的可能机制；同时在体分析NEDs中该蛋白表达水平对tau转基因小鼠病理及行为学的影响，从而明确PPP2R5C蛋白在AD发病过程中的可能作用，为揭示AD致病机制提供新的线索。

PPP2R5C protein was identified to be significantly decreased in plasma neuron-derived exosomes (NDEs) from both pre-symptomatic FAD and FAD patients in our previous study, which is negatively related with disease progression, indicating it’s a potential biomarker for AD. This finding was further confirmed in patients with sporadic AD and aMCI, suggesting that down- regulation of PPP2R5C in NDEs may be involved in AD pathogenesis at an early stage. PPP2R5C belongs to the regulatory subunit of Protein Phosphatase 2A (PP2A), which were responsible for dephosphorylation of tau protein. Considering all the above points, we hypothesize that PPP2R5C as a key regulatory subunit may modulate activity of PP2A in neuron, and down- regulation of PPP2R5C in NDEs may accelerate progression of AD through diverse pathways. In the present study, our aim is to investigate the role of PPP2R5C in NEDs in maintaining the physiological function of tau protein, microtubule structure and neuron activity. Then, we explore the possible mechanisms of PPP2R5C in regulating tau dephosphorylation and neuronal apoptosis. Meanwhile, lateral ventricle injection strategy will be performed to observe the behavior and histopathology alterations of tau transgenic mice after injecting NDEs containing different levels of PPP2R5C protein. All these might help us to understand the role of PPP2R5C protein in the pathogenesis of AD, providing new clues for pathogenesis and potential therapeutic targets of AD.