Atomic force microscopy of paired helical filaments isolated from the autopsied brains of patients with Alzheimer's disease and immunolabeled against microtubule-associated protein tau

Atomic force microscopy was employed to study the structural features of paired helical filaments isolated from autopsied brains of Alzheimer's disease patients. The identity of paired helical filaments was confirmed following a specific immunogold labeling using antibodies directed against the microtubule-associated protein tau, which is the main constituent of paired helical filaments. Computer-assisted analysis of high resolution, three-dimensional images allowed us to study the longitudinal and cross- sectional profiles of individual filaments. Vertical dimensions of filaments were assessed along these sectional profiles. The smallest vertical diameter (6.66 ± 0.78 nm) was obtained at the level of the greatest lateral profile (ie, 'loop'), while the greatest vertical diameter was two times larger (13.68 ± 1.46 nm) and was obtained at the level of the smallest lateral profile (ie, 'crossover'), of the filament. Based on the shapes of these sectional profiles and their vertical dimensions, paired helical filaments appeared to be composed of two identical integral subunits, each of a circular cross-sectional profile of ~7 nm in diameter, wound around one another in a left helical manner, with a 7-nm center-to-center separation. Half-period of this helix was estimated at 81.4 ± 2.1 nm. Serial cross- sectional profiles of paired helical filaments were further utilized to construct a theoretical model of their internal organization. This model suggests that each structural subunit of the paired helical filament incorporates at least four identical protofilaments.