Alzheimer paired helical filaments (PHFs) studied by high-resolution TEM: what can vertical Pt-C replication tell us about the organization of the pronase-digested PHF core?

Microsc Res Tech. 2005 Jul;67(3-4):196-209. doi: 10.1002/jemt.20198.

Abstract

Untreated paired helical filaments (PHFs) and pronase-digested PHF-core filaments were 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 (T) = 10.6 +/- 1.7 nm, and a helical turn period (L) = 78.6 +/- 13.4. The surfaces of the untreated PHF's fuzzy coat appears disorganized. The widths of the pronase-treated PHF-core filaments were significantly reduced (W(d) = 14.8 +/- 1.2 nm, T(d) = 5.7 +/- 1.0 nm, and L(d) = 75.4 +/- 17 nm). The surfaces of the untreated PHF contained approximately 1.1 nm strands, the same size as tau monomer ( approximately 1.0 nm). The pronase-digested PHF cores mostly contained approximately 1.6 +/- 0.3 nm strands although strand diameters ranged from 0.6-2.5 nm. The strands sometimes appear to be wrapped around the filament axis; less often, they appear to be roughly parallel to the PHF axis, and otherwise appear to be randomly oriented. Images of pronase-digested PHF core images are discussed in relation to the core's biochemical composition, its proposed beta structure, and structural subunit models. Images of the untreated and the pronase-digested PHF support a helical ribbon morphology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / pathology*
  • Freeze Drying
  • Humans
  • Male
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Neurofibrillary Tangles / chemistry
  • Neurofibrillary Tangles / ultrastructure*
  • Pronase / chemistry
  • Replica Techniques

Substances

  • Pronase