In light of these results, it is tempting to propose that cognitive defects in the hAPP NL/F mice with T2DM are the result of alterations at, at least, two different levels: directly dependent on the perturbations induced by amyloid peptide/oligomers over time (i.e., intracellular ionic imbalance) and directly dependent on the alteration induced by a particular external insult (i.e., γ-secretase inhibition/Tau aberrant phosphorylation in the T2DM condition). The gene discussed is MAPT; the disease is type 2 diabetes mellitus.