Congo red and thioflavin-T analogs detect Aβ oligomers

Izumi Maezawa, Hyun Seok Hong, Ruiwu Liu, Chun Yi Wu, R. Holland Cheng, Mei Ping Kung, Hank F. Kung, Kit S. Lam, Salvatore Oddo, Frank M. LaFerla, Lee Way Jin

Research output: Contribution to journalArticlepeer-review

172 Scopus citations

Abstract

Several small molecule ligands for amyloid-β (Aβ) fibrils deposited in brain have been developed to facilitate radiological diagnosis of Alzheimer's disease (AD). Recently, the build-up of Aβ oligomers (AβO) in brain has been recognized as an additional hallmark of AD and may play a more significant role in early stages. Evidence suggests that quantitative assessment of AβO would provide a more accurate index of therapeutic effect of drug trials. Therefore, there is an urgent need to develop methods for efficient identification as well as structural analysis of AβO. We found that some well established amyloid ligands, analogs of Congo red and thioflavin-T (ThT), bind AβO with high affinity and detect AβO in vitro and in vivo. Binding studies revealed the presence of binding sites for Congo red- and thioflavin-T-analogs on AβO. Furthermore, these ligands can be used for imaging intracellular AβO in living cells and animals and as positive contrast agent for ultrastructural imaging of AβO, two applications useful for structural analysis of AβO in cells. We propose that by improving the binding affinity of current ligands, in vivo imaging of AβO is feasible by a 'signal subtraction' procedure. This approach may facilitate the identification of individuals with early AD.

Original languageEnglish (US)
Pages (from-to)457-468
Number of pages12
JournalJournal of neurochemistry
Volume104
Issue number2
DOIs
StatePublished - Jan 1 2008

Keywords

  • Alzheimer
  • Amyloid
  • Imaging
  • Ligand
  • Oligomer
  • Small molecule

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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