Antibodies targeting the pT231 and pS396 epitopes of tau, with affinities of 1–4 nM, were evaluated in a primary neuron culture model of tau pathology, as well as in two distinct tau transgenic mouse models that develop prominent tau inclusions with aging that are very reminiscent of those seen in AD and related tauopathies. The gene discussed is MAPT; the disease is tauopathy.