The experience from clinical trials indicates that anti-Aβ immunotherapy could be effective in early/pre-clinical stages of AD， whereas at the late stages promoting the clearing of Aβ alone may be insufficient to halt the disease progression. At the same time， pathological tau correlates much better with the degree of dementia than Aβ deposition. Therefore， targeting pathological tau may provide a more promising approach for the treatment of advanced stages of AD. Recent data demonstrates that the N-terminal region of tau spanning aa 2-18 termed "phosphatase activation domain" that is normally hidden in the native protein in 'paperclip'-like conformation， becomes exposed in pathological tau and plays an essential role in the inhibition of fast axonal transport and in aggregation of tau. Hence， we hypothesized that anti-Tau monoclonal antibodies (mAb) may recognize pathological， but not normal tau at very early stages of tauopathy and prevent or decrease the aggregation of this molecule.