Rapid size-exclusion high performance liquid chromatography method for the quality control of amyloid-β oligomers

J Chromatogr A. 2021 Apr 26:1643:462024. doi: 10.1016/j.chroma.2021.462024. Epub 2021 Mar 18.

Abstract

Amyloid-β (Aβ) dysmetabolism is thought to be the main trigger for neurodegenerative events in Alzheimer's disease (AD). In particular, soluble Aβ oligomers (AβOs) are proposed as key mediators of synaptic and cognitive dysfunction in AD. Over the past few decades, AβOs prepared from synthetic Aβ have been widely applied in vitro and in vivo, the so-called chemical models of AD, uncovering their multiple neurotoxic mechanisms. However, the lack of a reliable quality control (QC) for synthetic AβOs may reflect poor experimental reproducibility. In keeping with this, we optimized and validated a rapid and reproducible SECHPLC method using fluorescence detection for the QC of synthetic AβOs. Our analytical method offers an unprecedent alternative to improve the reproducibility of AD chemical models.

Keywords: Amyloid-β; Oligomers; Quality control; SEC-HPLC; Validation.

MeSH terms

  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / analysis*
  • Animals
  • Chromatography, Gel / methods*
  • Chromatography, High Pressure Liquid
  • Humans
  • Hydrogen-Ion Concentration
  • Protein Multimerization*
  • Quality Control
  • Reproducibility of Results
  • Temperature

Substances

  • Amyloid beta-Peptides