MAPT and tauopathy: In summary, the present investigation not only confirms and extends the notion that extracellular tau is per se harmful for neurons [13, 23, 62] but also opens novel and potentially more effective therapeutic opportunities aimed at preventing the early impairment in synaptic plasticity and memory caused by one of the actually secreted [21, 27, 28] and, consequently, pathologically relevant N-terminal truncated species in human tauopathies.