In our previous study, we found that the accumulated htau increased STAT1 activity, while the activity of HNF1, HOX4C, PLAG1, SMUC, VDR, SF-1, and PIT1 decreased remarkably.26 STAT3 and STAT1 belong to the STAT protein family, and both are reported to play a role in cognitive deficits induced by Abeta.27–34 Herein, we investigated the effects of P301L-hTau accumulation on STAT3 activity, and if so, the role of STAT3 in P301L-hTau-induced cognitive deficits and the underlying molecular mechanisms. This evidence concerns the gene STAT3 and Cognitive impairment.