Figure 1. Experimental strategy to generate a mouse model of Alzheimer’s disease with a chronic reduction of PAK activity in the forebrain (A) dnPAK mice were crossed with 3xTg-AD or the corresponding non-transgenic mice (NonTg) yielding three genotypes: NonTg (-/-), 3xTg-AD (+/-) and 3xTg-AD-dnPAK (+/-) (B). Consistently, phosphorylation of PAK was significantly reduced in the frontal cortex of 18-month-old 3xTg-AD-dnPAK animals, confirming the inactivation of PAK. Actin served as an internal control for protein loading (N=12-13 mice for NonTg, N=19-21 mice for 3xTg-AD and N=16-17 mice for 3xTg-AD-dnPAK). Examples of Western blots were taken from the same immunoblot experiment for each primary antibody, on the same gel but run in a random order, and rearranged in the same order as the graphs (separated by black lines). O p<0.05, OO p<0.01, ***p<0.001, Tukey-Kramer post hoc test, one way ANOVA. Abbreviations: PAK: p21 activated kinase, dnPAK: dominant negative p21-activated kinase, pPAK: phospho-PAK; ROD, relative optical density.