In our study, HO2 treatment increased the expression of BDNF, NT‐3, and NT‐4/5 through the upregulation of MeCP2/p‐CREB activity (Figures 2 and 3), whereas siRNA‐mediated knockdown of MeCP2 or TrkB in the hippocampus blocked the therapeutic effects of HO2 on the cognitive deficits of Tg‐APP/PS1 mice (Figure 6). This evidence concerns the gene NTF4 and Cognitive impairment.