Paired Helical Filaments Are Twisted Ribbons Composed of Two Parallel and Aligned Components: Image Reconstruction and Modeling of Filament Structure Using Atomic Force Microscopy

To study the structure of Alzheimer paired helical filaments (PHF) we examined isolated detergent-insoluble PHF using atomic force microscopy with image reconstruction. The reconstructed AFM images of Alzheimer PHF most closely resembled ribbon-like helices with thin edges. The presence of a conspicuous furrow in the PHF midline indicated that PHF were composed of two distinctive strands. Our present conception of the overall configuration of PHF is consistent with that proposed by Crowther and Wischik in 1985 but includes an essential component of the prevailing modelthe presence of two strands. Thus, our new model of PHF structure, based on atomic force microscopy-derived data, indicates that the true structure of PHF is actually a hybrid of the prevailing PHF model and a thin helical ribbon.