PAIRED HELICAL FILAMENTS IN CORTICOBASAL DEGENERATION - THE FINE FIBRILLARY STRUCTURE WITH NANOVAN

Paired helical filaments (PHF) composed of hyperphosphorylated tau pro teins are characteristic findings in neurodegenerative disorders, incl uding Alzheimer's disease (AD) and corticobasal degeneration (CBD). Th e filaments in CBD differ from those in AD by a reduced number of tau isoforms and less stable ultrastructure. To further compare the ultras tructure of both filaments, we employed a novel staining reagent, Nano Van, as well as aurothioglucose and uranyl acetate. With commonly used uranyl acetate, both kinds of filaments appeared as twisted ribbons 1 5-20-nm and 21-23-nm wide, respectively, without significant internal substructure. With application of aurothioglucose, only few structural details were apparent. With NanoVan, AD filaments showed similar stru cture to that with uranyl acetate but CBD filaments displayed a highly heterogeneous appearance consistent with the dissociation of the 20-2 5-nm-wide filaments along two longitudinal axes. This was evident by t he presence of thinner, 12-13-nm-wide filaments and filaments that spl ayed into two 20-25-nm-wide components at one or both ends. Moreover, detection of a prominent, 7-8-nm-wide axial region distinguished up to four protofilaments per one filament. Each protofilament appeared to contain two 3-5-nm-wide fibrils separated by an approximately 1-nm-wid e axial region. The results suggest that 3-5-nm fibrils are the smalle st structural subunits of filaments in CBD and that NanoVan may be an unique reagent in detecting eight-fibril organization in these less st able filaments. (C) 1997 Elsevier Science B.V.