Effects of chronic masitinib treatment in APPPS1dE9 transgenic mice modeling Alzheimer’s disease

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Li, Tengfei | Martin, Elodie | Abada, Yah-Se | Boucher, Céline | Cès, Aurélia | Youssef, Ihsen | Fenaux, Grégory | Forand, Yona | Legrand, Annaelle | Nachiket, Nadkarni | Dhenain, Marc | Hermine, Olivier | Dubreuil, Patrice | Delarasse, Cécile | Delatour, Benoît

Edité par CCSD ; IOS Press -

International audience. 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 APPswe/PSEN1dE9 transgenic mice modeling Alzheimer's disease restored normal spatial learning performance while having no impacts on amyloid-␤ loads nor on neuroinflammation. However, masitinib promoted a recovery of synaptic markers. Complete genetic depletion of mast cells in APPswe/PSEN1dE9 mice similarly rescued synaptic impairments. Conclusion: These results underline that masitinib therapeutic efficacy might primarily be associated with a synaptoprotective action in relation with mast cells inhibition.

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