We next investigated the role of PS in human tau pathology in novel PS1 cKO;Tau (PS1 f/f;CamKIIα-Cre;Tau) and PS cKO;Tau (PS1 f/f;PS2−/−;CamKIIα-Cre;Tau) mice obtained by crossing PS1 cKO and PS cKO mice with mutant Tau transgenic (PS19) mice expressing the FTD-linked P301S mutation in excitatory neurons [73]. This evidence concerns the gene MAPT and frontotemporal dementia.