Communication to the Editor

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

  1. Ben Keshet,
  2. In Hong Yang†,
  3. Theresa A. Good*

Article first published online: 10 FEB 2010

DOI: 10.1002/bit.22691

Issue

Biotechnology and Bioengineering

Biotechnology and Bioengineering

Volume 106, Issue 2, pages 333–337, 1 June 2010

Additional Information

How to Cite

Keshet, B., Yang, I. H. and Good, T. A. (2010), Can size alone explain some of the differences in toxicity between β-amyloid oligomers and fibrils?. Biotechnol. Bioeng., 106: 333–337. doi: 10.1002/bit.22691

Author Information

  1. Chemical and Biochemical Engineering, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250; telephone: 410-455-3405; fax: 410-455-1049

  1. †

    Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD.

*Chemical and Biochemical Engineering, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, Maryland 21250; telephone: 410-455-3405; fax: 410-455-1049.

Publication History

  1. Issue published online: 16 APR 2010
  2. Article first published online: 10 FEB 2010
  3. Accepted manuscript online: 10 FEB 2010 12:00AM EST
  4. Manuscript Accepted: 25 JAN 2010
  5. Manuscript Revised: 15 JAN 2010
  6. Manuscript Received: 27 OCT 2009

Funded by

  • NIH. Grant Number: R01 NS042686
  • NSF. Grant Number: CBET 0828009

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Keywords:

  • Alzheimer's;
  • oligomer;
  • protofibril;
  • diffusion;
  • structure;
  • biological activity

Abstract

β-Amyloid (Aβ) peptide is believed to play a key role in the mechanism of Alzheimer's disease (AD). Aβ tends to aggregate to form amyloid fibrils. A variety of evidence indicates that Aβ aggregates are toxic in vitro and in vivo. An early “Aβ hypothesis” postulated that AD was the consequence of neuron death induced by insoluble deposits of large Aβ fibrils. Newer findings indicate that small soluble Aβ oligomers are the neurotoxic species, yet their structure is still unknown. Many researchers have tried to probe the differences in molecular structure between Aβ 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 Aβ 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 Aβ oligomers and fibrils have identical molecular structures, it highlights the possibility that simple physical phenomena may contribute to the biological processes induced by Aβ. Biotechnol. Bioeng. 2010;106: 333–337. © 2010 Wiley Periodicals, Inc.

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