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

A novel monoclonal antibody DC39N1 specific for tau protein N-terminal insert N1 (residues 45-73) was developed. Species analysis revealed that monoclonal antibody DC39N1 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 N1 insert. DC39N1 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 N1 insert during evolution of neurofibrillary degeneration from early to late stages of Alzheimer's disease.