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 and 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 Aß 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.
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