Ultrastructural aspects of neurofibrillary tangle formation in aging and Alzheimer's disease

Neurofibrillary tangles, one of the neuropathological signs of Alzheimer's disease, are frequently present in brains of aged nondemented people. Ultrastructurally, neurofibrillary tangles appear as paired helical and straight filaments. Both types of filaments, made of hyperphosphorylated tau protein, are present in neurons with neurofibrillary tangles. Neurons with neurofibrillary tangles have been described to undergo an evolution, starting with the accumulation of hyperphosphorylated tau, followed by the progressive appearance of both types of filaments, and ending in the death of the neuron. We ultrastructurally studied this evolution, using immunocytochemistry with an antibody against phosphorylated tau protein, in both nondemented aged and Alzheimer's disease brains. No differences were found between nondemented and demented brains, thus indicating the occurrence of the same process in both cases. Our results also suggest that hyperphosphorylated tau protein first appears as granular material, which becomes organized into short and disordered paired helical filaments. These filaments elongate and gradually become arranged into bundles whose core regions are occupied by straight filaments.