Scanning electron microscopical study of the neurofibrillary tangles of Alzheimer's disease

Neurofibrillary tangles (NFTs) have been ultrastructurally studied by various methods, leading to several three-dimensional models of paired helical filaments (PHFs). In this study, we present the scanning electron microscopic findings of NFTs in an autopsy case of Alzheimer's disease and clarify the three-dimensional structures of NFTs. NFTs were clearly defined in freeze-cracked nerve cells and consisted of two types of filamentous structures, straight and helical filaments. Straight filaments measured from 20 to 25 nm in diameter and had a smooth surface. They were slightly bent but mostly straight with no constrictions. One type of straight filaments ran in a bundle in the same direction, another was intertwined to each other. Most of the helical profiles of filaments usually measured about 28 nm in diameter, with a distance of 100 nm between periodic constrictions. They seemed to consist of a pair of isodiametric filaments of 10 nm in diameter. In addition, two unusual types of helical filaments were occasionally observed. One comprised thick filaments of about 38 nm in diameter, with a distance of 100 nm between constrictions; these helical filaments appeared to consist of two or more strands. The other comprised thin helical filaments of about 20 nm in diameter and regularly constricted at an interval of 50 nm. All types of the helical filaments examined in this case were leotropic. This result supports a protofilament model of PHFs. Scanning electron microscopy using the freeze-cracked and maceration method is a useful and simple method for three-dimensional observation of the filamentous structures in NFTs.