MAPT and Alzheimer disease: In addition to the evaluated AD cases, each likely with a distinct underlying disease cause, we found overexpression of the human T40 isoform of tau (4R2N), introduction of an APP mutant (APP duplication) in neuronal cells, or overexpression of the human T34 isoform of tau (1N4R) with the P301S mutation in mouse brains (i.e., PS19 mice), to each promote functional imbalances in some, if not all, of these synaptic protein networks through the switch of the chaperome into epichaperomes (Fig. 4).