Meanwhile, due to an increase in studies providing evidence of a causal role of brain hypometabolism and mitochondrial bioenergetic deficits (Yao et al., 2011), a subsequent increase in studies is seeking to explain how mitochondrial complex I (NADH:ubiquinone oxidoreductase—the first and the largest complex of the electron transport chain (ETC)) and complex IV (cytochrome c oxidase – the last enzyme in the respiratory ETC) offered the most profound reduction in levels of Aβ, phosphor-tau, and cognitive decline in three animal models of familial AD (Moreira et al., 2010; Zhang et al., 2015). This evidence concerns the gene MAPT and Mental deterioration.