Alzheimer's disease is characterized by progressive memory loss and deterioration of cognitive functions. The presence of neurofibrillary tangles in the hippocampal areas (perforant pathway) correlates with cognitive impairment. Pathological processing of tau protein is characterized by post-translational changes such as hyperphosphorylation and truncation, which favour conformational changes within tau. These conformational changes can be regional (dependent on phosphorylation) or structural (depending on regional conformational changes and truncation). Through immunohistochemical and immunofluorescence staining in hippocampus Alzheimer disease brains and quantification in tissue stained with TG3 antibody and analysed by confocal microscopy, we have been able to demonstrate that TG3 correlates with cognitive impairment. In the process of tangle evolution, TG3 is present in pre-tangle. This epitope of the TG3 antibody was very stable to proteolytic processing by caspase-3; truncation is evidenced by the TauC-3 antibody. The entorhinal cortex showed high sensitivity to neurodegeneration and pathological tau processing.