阿尔兹海默病(Alzheimer's disease, AD)是以进行性认知功能衰退为特征的老年性神经退行性疾病。AD的重要病因之一是β淀粉样肽（Aβ）在大脑的神经元内外积累。神经元内Aβ积累发生在AD早期，在突触损伤、淀粉样斑块形成、神经元死亡中的作用越来越受到重视。但是Aβ在神经元内积累是如何发生、如何引起突触损伤和神经元死亡的分子细胞机制还不清楚。我们前期结果显示在Aβ表达果蝇中，下调efr3a的果蝇同源基因rbo的功能或表达量能显著减少神经元内Aβ的积累、减轻突触传递障碍、减少神经元的死亡。为进一步明确efr3a基因在AD中的作用及细胞分子机制，我们拟在AD模型小鼠（APP/Psn1转基因）中研究条件性敲除efr3a基因后是否改善AD小鼠的神经退行性病理变化及学习记忆障碍，是否影响神经元内Aβ积累，并研究其细胞分子机制。如获预期结果，可为AD的诊治提供新的潜在靶点或途径。

Alzheimer's Disease (AD)is characterized by a progressive loss of learning and memory abilities in elderly people. One of the major causes of AD is the accumulation of beta amyloid (Aβ) in the brain. Aβ accumulates both intraneuronally and extracellularly, but intraneuronal Aβ accumulation occurs earlier and may play an important role in synaptic impairment,formation of senile plaque and neuron death in AD. However, the cellular and molecular mechanisms of neuronal Aβ accumulation and its role in neurodegeneration are not clear. In our unpublished study,we developed a Drosophila model in which Aβ accumulates intraneuronally and caues a series of age-dependent synaptic and axonal changes. In this model, we found that insufficiency of rbo gene,the Drosophila homolog of efr3a, reduced intraneuronal Aβ accumulation,ameliorated the synaptic deficit and reduced neuron death. Here we propose to investigate the effect of conditional efr3a knockout on the neuropathological and cognitive changes in APP/Psn double transgenic mice, and study how RBO/Efr3a regulates/mediates intraneuronal Aβ accumulation. This study may provide potential therapeutic target for AD.