Characterization by atomic force microscopy of Alzheimer paired helical filaments under physiological conditions

Biophys J. 2004 Jan;86(1 Pt 1):517-25. doi: 10.1016/S0006-3495(04)74130-2.

Abstract

Paired helical filaments (PHF) is an aberrant structure present in the brain of Alzheimer's disease patients which has been correlated with their degree of dementia. In order to determine the structure of PHF, several studies have been performed using atomic force microscopy (AFM). However, those studies have the limitation that they have not been done in solution and the sample could be far from the real physiological conditions. In this work we present an AFM analysis of PHF in liquid environment and we compare that analysis with that performed in dry conditions. PHF imaging in liquid was only possible by using jumping mode AFM as the imaging technique. Jumping mode AFM images of PHF in solution show first, a notable increase in the absolute values of the height of the filament, and second, a smaller ratio between the height measured at the upper and at the lower part of the PHF. Direct comparison of the experimental data with structural models has been performed. From this we conclude that the PHF structure is compatible with two coupled ribbons with an overall height of 20 nm and a width of 10 nm.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Fluids / chemistry
  • Computer Simulation
  • Microscopy, Atomic Force / methods*
  • Models, Molecular*
  • Neurofibrillary Tangles / chemistry*
  • Neurofibrillary Tangles / ultrastructure*
  • Protein Conformation
  • Protein Structure, Secondary
  • Solutions
  • tau Proteins / chemistry*
  • tau Proteins / ultrastructure*

Substances

  • Solutions
  • tau Proteins