We discuss three important aspects that are directly concerned by the AAV-models: (i) the mechanism by which protein tau destroys pyramidal neurons; (ii) the information content of the experimental models for human disease, i.e. primary tauopathies and AD; (iii) the marked difference with classical transgenic mice that have amyloid deposits and/or tangles with minimal neurodegeneration. The gene discussed is MAPT; the disease is Alzheimer disease.