Liu Kefu, Aierken Ailikemu, Liu Mengyao, Parhat Nazakat, Kong Wei, Yin Xingyu, Liu Gang, Yu Ding, Hong Jie, Ni Junjun, Quan Zhenzhen, Liu Xiaoyun, Ji Simei, Mao Jian, Peng Weijun, Chen Chao, Yan Yan, Qing Hong
MOE Key Laboratory of Rare Pediatric Diseases & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410083, Hunan, China.
Key Laboratory of Molecular Medicine and Biotherapy, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
iScience. 2024 Feb 20;27(3):109281. doi: 10.1016/j.isci.2024.109281. eCollection 2024 Mar 15.
Alzheimer's disease (AD) is the most common neurodegenerative disease often associated with olfactory dysfunction. Aβ is a typical AD hall marker, but Aβ-induced molecular alterations in olfactory memory remain unclear. In this study, we used a 5xFAD mouse model to investigate Aβ-induced olfactory changes. Results showed that 4-month-old 5xFAD have olfactory memory impairment accompanied by piriform cortex neuron activity decline and no sound or working memory impairment. In addition, synapse and glia functional alteration is consistent across different ages at the proteomic level. Microglia and astrocyte specific proteins showed strong interactions in the conserved co-expression network module. Moreover, this interaction declines only in mild cognitive impairment patients in human postmortem brain proteomic data. This suggests that astrocytes-microglia interaction may play a leading role in the early stage of Aβ-induced olfactory memory impairment, and the decreasing of their synergy may accelerate the neurodegeneration.
阿尔茨海默病（AD）是最常见的神经退行性疾病，常伴有嗅觉功能障碍。β淀粉样蛋白（Aβ）是典型的AD标志性物质，但Aβ诱导的嗅觉记忆分子改变仍不清楚。在本研究中，我们使用5xFAD小鼠模型来研究Aβ诱导的嗅觉变化。结果显示，4个月大的5xFAD小鼠存在嗅觉记忆障碍，伴有梨状皮质神经元活动下降，且无听觉或工作记忆障碍。此外，在蛋白质组学水平上，不同年龄的突触和神经胶质细胞功能改变是一致的。小胶质细胞和星形胶质细胞特异性蛋白在保守的共表达网络模块中显示出强烈的相互作用。此外，在人类死后大脑蛋白质组学数据中，这种相互作用仅在轻度认知障碍患者中下降。这表明星形胶质细胞-小胶质细胞相互作用可能在Aβ诱导的嗅觉记忆障碍早期起主导作用，它们协同作用的降低可能会加速神经退行性变。
