A standardized and biocompatible preparation of aggregate-free amyloid beta peptide for biophysical and biological studies of Alzheimer's disease

Protein Eng Des Sel. 2011 Sep;24(9):743-50. doi: 10.1093/protein/gzr020. Epub 2011 May 11.

Abstract

We provide a validated and rapid protocol for the solubilization of amyloid β-peptide (Aβ). This procedure involves sequential solubilization using structure-breaking organic solvents hexafluoroisopropanol and DMSO followed by column purification. The low solubility and tendency of Aβ to aggregate considerably impede the in vitro handling and biophysical or biological investigation of Aβ, despite the interest in this peptide because of its implication in Alzheimer's disease. The main advantage of the proposed protocol over others is that it results in standardized aggregate-free Aβ peptide samples that are biocompatible for cell culture studies and yield reproducible aggregation kinetics and cytotoxicities. This three-step protocol also enables the co-solubilization of the longer Aβ42 variant with Aβ40 in ratios relevant to Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / metabolism
  • Benzothiazoles
  • Biomedical Research / standards
  • Cell Line, Tumor
  • Cytological Techniques / standards*
  • Humans
  • Indicators and Reagents
  • Kinetics
  • Microscopy, Electron, Transmission
  • Nuclear Magnetic Resonance, Biomolecular
  • Reproducibility of Results
  • Solubility
  • Spectrometry, Fluorescence
  • Thiazoles / chemistry

Substances

  • Amyloid beta-Peptides
  • Benzothiazoles
  • Indicators and Reagents
  • Thiazoles
  • thioflavin T