MAPT and Cognitive impairment: Although functional behavioral studies are established as the gold standard for assessing drug efficacy, most of the cognitive deficits occur in the late stage of AD, triggered by Aβ deposits and tau NFT aggregates implicated in hyperexcitation [56] and/or impaired synaptic inhibition [65,66], neuroinflammation [8], and an increase in pro-apoptotic metalloproteinases [67], among other mechanisms.