Background:Masitinib is a selective tyrosine kinase inhibitor that modulates mast cells activity. A previous phase II study reported a cognitive effect of masitinib in patients with Alzheimer’s disease. Objective:We aimed to shed light on the mode of action of masitinib in Alzheimer’s disease. Methods/Results:We demonstrated here that chronic oral treatment of APPPS1dE9 transgenic mice modeling Alzheimer’s disease restored normal spatial learning performance while having no impacts on amyloid-β loads nor on neuroinflammation. However, masitinib promoted a recovery of synaptic markers. Complete genetic depletion of mast cells in APPPS1dE9 mice similarly rescued synaptic impairments. Conclusion:These results underline that masitinib therapeutic efficacy might primarily be associated with a synapto-protective action in relation with mast cells inhibition.

中文翻译：

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慢性马赛替尼治疗对模拟阿尔茨海默氏病的APPswe / PSEN1dE9转基因小鼠的影响。

背景：马赛替尼是一种选择性酪氨酸激酶抑制剂，可调节肥大细胞活性。之前的II期研究报告了马赛替尼对阿尔茨海默氏病患者的认知作用。目的：我们旨在阐明马赛替尼在阿尔茨海默氏病中的作用方式。方法/结果：我们在这里证明，长期口服APPPS1dE9转基因小鼠模拟阿尔茨海默氏病，可恢复正常的空间学习性能，而对β-淀粉样蛋白负荷或神经炎症无影响。但是，马赛替尼可促进突触标记物的恢复。APPPS1dE9小鼠中肥大细胞的完全遗传耗竭同样挽救了突触损伤。结论：