Effects of Chronic Masitinib Treatment in APPPS1dE9 Transgenic Mice Modeling Alzheimer's Disease.

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.