Alzheimer paired helical filaments, untreated and pronase digested, studied by vertical platinum-carbon replication...

Untreated paired helical filaments (PHF) and pronase treated PHF filaments have been stereoscopically imaged with a freeze-drying vertical platinum-carbon replication preparation method for TEM. The untreated PHF have an average wide region, W = 22.8 +/- 2.4 nm, a narrow region width, T = 10.6 +/- 1.7 nm, and a helical turn period, L = 78.6 +/- 13.4. The widths of the pronase treated PHF were significantly reduced and had average measurements of W = 14.8 +/- 1.2 nm, T = 5.7 +/- 1.0 nm, with the helical period unchanged, L = 75.4 +/- 17 nm. The surfaces of the untreated PHF contained approximately 1.0 and approximately 0.4 nm strands, the size of normal and denatured tau monomer. The pronase treated PHF contained approximately 1.0 and approximately 0.4 nm strands as well as approximately 2.0 nm strands. The stereoscopic images of the untreated and the pronase digested PHF do not support a double helical morphology for the PHF. The PHF appear to be long helical ribbons. The approximately 1.0 and approximately 2 nm substructure has been organized both parallel and orthogonal to the PHF-core axis for distances less than 80 nm. The most frequent structural appearance is of a disorganized PHF core. The surfaces of the untreated PHF also have a similar disorganized appearance.