Ms. Pollanen et al., TWISTED RIBBON STRUCTURE OF PAIRED HELICAL FILAMENTS REVEALED BY ATOMIC-FORCE MICROSCOPY, The American journal of pathology, 144(5), 1994, pp. 869-873
Progressive deposition of phosphorylated tau into the paired helical f
ilaments (PHF) that compose neurofibrillary tangles, dystrophic neurit
es, and neuropil threads is an obligate feature of Alzheimer's disease
. Tbe standard model of PHF structure, derived from electron microscop
ic studies, suggests that two 8- to 10-nm filaments each composed of t
hree to four protofilaments are wound into a helix with a maximal diam
eter of similar to 20 nm and a half period of 65 to 80 nm. However, re
cent vertical platinium-carbon replicas of PHF more closely resemble a
thin helical ribbon without constitutive protofilaments. Here we repo
rt that native PHF imaged with an atomic force microscope appear as tw
isted ribbons rather than the generally accepted structure derived fro
m electron microscopic studies. These data imply that the assembly of
PHF is not due to the twisting of pair-wise filaments but rather the h
elical winding of self-associated tau molecules arranged into a flatte
ned structure. Future structural models of PHF should be based on quan
titative data obtained from imaging techniques, such as scanning probe
microscopy, which do not require harsh specimen preparation procedure
s.