BDNF and metabolic disease: Particularly, mitochondrial Ca2+ overloading results in an increase of ROS production in mitochondria [48], the oxidative stress leads to abnormalities in the cell calcium storage, and the ability to control oxidative stress and respond to metabolic disorder links the AD-causing gene mutations to the disease process [49], while cell death was increased as were Bax levels with a concomitant decrease in Bcl-2 in the hippocampus of the 3xTg AD mouse, showing deficiencies in cognitive functions due to a decrease in BDNF, PSD95, and synaptophysin expression [50–52].