Can size alone explain some of the differences in toxicity between beta-amyloid oligomers and fibrils?

Biotechnol Bioeng. 2010 Jun 1;106(2):333-7. doi: 10.1002/bit.22691.


beta-Amyloid (Abeta) peptide is believed to play a key role in the mechanism of Alzheimer's disease (AD). Abeta tends to aggregate to form amyloid fibrils. A variety of evidence indicates that Abeta aggregates are toxic in vitro and in vivo. An early "Abeta hypothesis" postulated that AD was the consequence of neuron death induced by insoluble deposits of large Abeta fibrils. Newer findings indicate that small soluble Abeta oligomers are the neurotoxic species, yet their structure is still unknown. Many researchers have tried to probe the differences in molecular structure between Abeta oligomers, protofibrils, and fibrils that give rise to their unique toxicities, but with limited success. In this report, we examine the hypothesis that differences in the toxicity of different aggregated Abeta species are the result of differences in species concentration and diffusivity. Using a simple mathematical analysis based on the assumption of a diffusion-limited reaction, we demonstrate that near 10-fold differences in toxicity between spherical oligomers and fibrils can be explained from size and concentration arguments. While this work does not suggest that Abeta oligomers and fibrils have identical molecular structures, it highlights the possibility that simple physical phenomena may contribute to the biological processes induced by Abeta.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / toxicity
  • Amyloid beta-Peptides / ultrastructure
  • Computer Simulation
  • Models, Biological*
  • Models, Chemical*
  • Models, Molecular*
  • Molecular Conformation
  • Structure-Activity Relationship


  • Amyloid beta-Peptides