All together the data presented in this study, obtained by using a non-Tg model of AD, demonstrated that oxidative stress, taking place as a consequence of pro-oxidant enzymes (i.e., iNOS and Nox2) activation, along with the previously showed deficit of TGF-β1, represents one of the neurobiological links between depression and AD. The gene discussed is NOS2; the disease is major depressive disorder.