First insert of tau protein is present in all stages of tau pathology in Alzheimer's disease.

A novel monoclonal antibody DC39NI specific for tau protein N-terminal insert NI (residues 45-73) was developed. Species analysis revealed that monoclonal antibody DC39NI did not recognize tau proteins derived from rat, mouse, bovine, swine and rabbit brain tissues and is human tau protein specific. The antibody recognized all and only those human tau isoforms that contain a tau NI insert. DC39NI epitope on paired helical filaments from the brain of patients with Alzheimer's disease is phosphorylation independent. Immunohistochemical analysis of Braak stages with novel antibody revealed the presence of tau aminoterminal NI insert during evolution of neurofibrillary degeneration from early to late stages of Alzheimer's disease.