Transthyretin binding to A-Beta peptide--impact on A-Beta fibrillogenesis and toxicity

FEBS Lett. 2008 Mar 19;582(6):936-42. doi: 10.1016/j.febslet.2008.02.034. Epub 2008 Feb 22.

Abstract

It has been suggested that transthyretin (TTR) is involved in preventing A-Beta fibrillization in Alzheimer's disease (AD). Here, we characterized the TTR/A-Beta interaction by competition binding assays. TTR binds to different A-Beta peptide species: soluble (Kd, 28 nM), oligomers and fibrils; diverse TTR variants bind differentially to A-Beta. Transmission electron microscopy (TEM) analysis demonstrated that TTR is capable of interfering with A-Beta fibrillization by both inhibiting and disrupting fibril formation. Co-incubation of the two molecules resulted in the abolishment of A-Beta toxicity. Our results confirmed TTR as an A-Beta ligand and indicated the inhibition/disruption of A-Beta fibrils as a possible mechanism underlying the protective role of TTR in AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / antagonists & inhibitors*
  • Amyloid / ultrastructure
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / toxicity*
  • Binding, Competitive
  • Cell Line
  • Humans
  • Microscopy, Electron, Transmission
  • Prealbumin / chemistry*

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Prealbumin