To investigate if Alzheimer paired helical filaments (PHF) closely res
emble twisted ribbons, as indicated by recent high-resolution ultrastr
uctural studies, we compared physical models of twisted ribbons with e
lectron microscopic images of PHF Uranyl-acetate-stained, isolated PHF
with one or two helical turns were compared with scale models of twis
ted ribbons with one and two helical turns rotated at different angles
. The various rotations of the twisted ribbon model corresponded well
with the different orientations of randomly dispersed PHF. The electro
n-dense regions of individual PHF turns previously thought to represen
t a cross-over site of paired filaments corresponded to the edge of th
e twisted ribbon when the ribbon was oriented perpendicular to the fil
ament axis. These data indicate that the overall configuration of PHF
is a twisted ribbon but does not exclude possible configuration restri
ctions due to an ordered arrangement of sub-units.