In the 1960s, electron microscopy of tissue sections was used to investigate the fine structure of neurofibrillary tangles in the Alzheimer's disease (AD) brain. Bundles of abnormal cytoplasmic filaments were observed in nerve cell bodies and their processes (Kidd 1963, 1964; Terry 1963; Terry et al. 1964). In 1963, Michael Kidd described the characteristic paired helical nature of the majority of filaments. He named the "paired helical filament" (PHF) because it appears to consist of two filaments wound helically around one another, with a longitudinal spacing between crossovers of about 80 nm and a width of 30 nm at the widest point and 15 nm at the narrowest (Fig. 1). There was discussion about the molecular nature of the PHF, with some arguing that it was made of neurofilaments (Terry 1963; Terry et al. 1964), and Kidd himself favoring the view that it was unrelated to the normal cytoskeleton (Kidd 1963, 1964). Also found in the neurofibrillary tangles of AD, as a minority species, is the so-called straight filament
(SF), a filament about 15 nm wide that does not exhibit the modulation in width shown by the PHF (Hirano et al. 1968; Fig. 1).
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