QIAD assay for quantitating a compound's efficacy in elimination of toxic Aβ oligomers

Sci Rep. 2015 Sep 23:5:13222. doi: 10.1038/srep13222.

Abstract

Strong evidence exists for a central role of amyloid β-protein (Aβ) oligomers in the pathogenesis of Alzheimer's disease. We have developed a fast, reliable and robust in vitro assay, termed QIAD, to quantify the effect of any compound on the Aβ aggregate size distribution. Applying QIAD, we studied the effect of homotaurine, scyllo-inositol, EGCG, the benzofuran derivative KMS88009, ZAβ3W, the D-enantiomeric peptide D3 and its tandem version D3D3 on Aβ aggregation. The predictive power of the assay for in vivo efficacy is demonstrated by comparing the oligomer elimination efficiency of D3 and D3D3 with their treatment effects in animal models of Alzheimer´s disease.

MeSH terms

  • Alzheimer Disease / pathology*
  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Carrier Proteins / pharmacology
  • Catechin / analogs & derivatives
  • Catechin / pharmacology
  • Disease Models, Animal
  • Ferredoxin-NADP Reductase / pharmacology
  • Humans
  • Inositol / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Mice, Transgenic
  • Oligopeptides / pharmacology
  • Protein Aggregation, Pathological / drug therapy*
  • Taurine / analogs & derivatives
  • Taurine / pharmacology

Substances

  • Amyloid beta-Peptides
  • Carrier Proteins
  • D3 peptide
  • Oligopeptides
  • affibody protein ZAbeta3
  • Taurine
  • scyllitol
  • Inositol
  • tramiprosate
  • Catechin
  • epigallocatechin gallate
  • Ferredoxin-NADP Reductase