Immunological demonstration of tau protein in neurofibrillary tangles of Alzheimer's disease

Neurofibrillary tangles are one of the neuropathological hallmark of Alzheimer's disease, described early as part of the pathological criteria of the disease. Ultrastuctural studies in the sixties showed their unusual features but their molecular composition was not unraveled before the mid-eighties. Initial biochemical studies suggested that they were composed of modified unidentified brain proteins, and several immunocytochemical studies suggested that they contained polypeptides cross-reactive with antibodies to cytoskeletal proteins. In 1985, we demonstrated that neurofibrillary tangles were immunolabelled by antibodies to the microtubule-associated protein tau and that antibodies raised to neurofibrillary tangles cross-reacted with tau proteins. These results were soon confirmed independently in several laboratories. Further studies were devoted to the analysis of tau post-translationnal modifications in the affected tissues and in cellular and animal models.