Disease-modifying benefit of Fyn blockade persists after washout in mouse Alzheimer's model

Alzheimer's disease remains without a disease-modifying therapy that improves symptoms after therapy withdrawal. Because no investigational agents have demonstrated disease-modifying effects clinically, we tested whether the Fyn inhibitor, saracatinib, provides persistent improvement in a transgenic model. Aged APPswe/PS1 Delta E9 mice were treated with saracatinib or memantine for 4 weeks and spatial memory improved to control levels. After drug washout, there was sustained rescue of both memory function and synapse density by saracatinib, but a loss of benefit from memantine. These data demonstrate a disease modifying persistent benefit for saracatinib in a preclinincal Alzheimer's model, and distinguish its action from that of memantine. (C) 2017 Elsevier Ltd. All rights reserved.