Next, in order to correlate the observed behavioral effects with possible alterations of the tau protein, we performed a biochemical characterization of human tau in AAV-WT and AAV-P301S mice. The expression level of tau in the mouse forebrain was assessed at different ages by western blotting in total brain homogenates. Using an antibody that recognizes both mouse and human tau (tau5), we observed an increase in the expression of a tau species with an apparent molecular weight of approximately 55 kDa, which indeed corresponds to 4R0N human tau (Supplementary Fig. S1). This isoform is also abundantly present in protein extracts from the neocortex of an Alzheimer’s patient and of an unaffected control. Compared to the level of endogenous tau in the forebrain of a mouse injected with the control AAV-maxFP vector, the amounts of total tau found in the AAV-WT and AAV-P301S mice were nearly doubled.