LncRNA在AD中的作用日益突显，lncRNA失调是否引发突触可塑性异常及学习记忆障碍，目前鲜有报道。前期工作，我们发现AK013786在AD模型小鼠中表达随年龄递增，AK013786敲除（AK KO）小鼠的学习记忆优于对照组。AK013786过表达可降低海马脑区的突触可塑性，而AK KO小鼠的突触可塑性优于野生对照组。此外，syn2a的含量可被AK013786所下调，AD患者海马脑区syn2的表达亦显著降低。据此推测，AK013786可能通过下调syn2a参与AD学习记忆过程。本项目拟1）明确AK013786、syn2a的表达与认知的相关性；2）揭示AK013786、syn2a对AD模型小鼠电生理、行为学的影响；3）阐明AK013786、syn2a在AD中被调控的分子机制。该项目将丰富lncRNA在不同脑区的作用，为lncRNA改善AD学习记忆能力提供理论依据和潜在的治疗靶点。

The role of lncRNA in AD is increasingly prominent. Currently, there are few reports on whether the dysregulation of lncRNA causes abnormal synaptic plasticity and disorders of learning and memory. In the previous work, we found that the expression of AK013786 increased with age in AD model mice, and AK013786 knockout (AK KO) mice had better learning and memory than the control group. AK013786 overexpression reduced synaptic plasticity in the hippocampus, and AK KO mice had better synaptic plasticity than the wild control group. In addition, the content of syn2a could be down-regulated by the overexpression of AK013786, and the expression of syn2 in the hippocampus of AD patients was also significantly decreased. It is speculated that AK013786 may participate in AD learning and memory process by down-regulating syn2a. This project plans to 1)clarify the correlation between the expression of AK013786/syn2a and cognition; 2) reveal the effects of AK013786 and syn2a on electrophysiology and behavior in AD model mice; 3) elucidate the molecular mechanism of AK013786 and syn2a regulated in AD. This project will enrich the roles of lncRNA in different brain regions, and provide a theoretical basis and potential therapeutic target for lncRNA to improve the learning and memory ability of AD.