Tau protein immunoreactivity in dementia of the Alzheimer type: II. Electron microscopy and pathogenetic implications. Effects of fixation on the morphology of the Alzheimer's abnormal filaments.

I have used Tau-1 and Tau-2, two monoclonal antibodies against tau protein, to study at the electron microscopic level the tau immunoreactivity in 8 cases with dementia of the Alzheimer type, using the peroxidase-antiperoxidase technique and formalin-fixed autopsy and biopsy brain tissues. In neurons and astrocytes, excessive amounts of tau immunoreactivity were noted in association with ribosomes. The Alzheimer's abnormal filaments in neurofibrillary tangles in neuronal perikarya, in senile plaques, and in a multitude of abnormal neuropil neurites were frequently stained intensely. However, many neurons contained either stained ribosomes only or stained ribosomes and unstained abnormal filaments both scattered and in neurofibrillary tangles. In all locations, the immunostained abnormal filaments were straight without appreciable periodic constrictions and, on cross-section, had a tubular appearance with stained walls, frequently demonstrable unstained lumens and an accentuation of staining intensity at the periphery. In addition, conventional electron microscopy showed that formalin-fixed and glutaraldehyde-fixed neurofibrillary tangles were made of compactly arranged straight filaments and loosely arranged paired helical filaments, whereas osmium tetroxide-fixed neurofibrillary tangles were made almost exclusively of paired helical filaments. These findings suggest that: (a) localization of excessive tau immunoreactivity with ribosomes might be the primary event and association of detectable tau immunoreactivity with already assembled filaments might be an epiphenomenon; and (b) the mode of fixation and subsequent preparatory procedures might alter the morphology of the Alzheimer's abnormal filaments.