MAPT and early-onset autosomal dominant Alzheimer disease: Besides, the fact that 12A12mAb does not change the expression level of full-length tau but selectively reduces the endogenously produced 20–22 kDa tau fragment in both Alzheimer’s disease strains, as we showed in western blotting Figs 2 and 3, further strengthens the notion that a local conformational element (i.e. sequence- and structure-based immunoreactive epitope) is more likely to underlie its in vivo specificity in targeting the neo-epitope of the N-derived truncated pathological tau specie(s), both in human and mouse.