Simultaneous measurement of a range of particle sizes during Aβ1-42 fibrillogenesis quantified using fluorescence correlation spectroscopy

Judith J. Mittag, Silvia Milani, Dominic Walsh, Joachim O. Rädler, Jennifer J. McManus*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

17 Citations (Scopus)

Abstract

Low molecular weight oligomers of amyloid beta (Aβ) are important drivers of Alzheimer's disease. A decrease in Aβ monomer levels in human cerebrospinal fluid (CSF) is observed in Alzheimers' patients and is a robust biomarker of the disease. It has been suggested that the decrease in monomer levels in CSF is due to the formation of Aβ oligomers. A robust technique capable of identifying Aβ oligomers in CSF is therefore desirable. We have used fluorescence correlation spectroscopy and a five Gaussian distribution model (5GDM) to monitor the aggregation of Aβ1-42 in sodium phosphate buffer and in artificial cerebrospinal fluid (ACSF). In buffer, several different sized components (monomer, oligomers, protofibrils and fibrils) can be identified simultaneously using 5GDM. In ACSF, the faster kinetics of fibrillogenesis leads to the formation of fibrils on very short timescales. This analysis method can also be used to monitor the aggregation of other proteins, nanoparticles or colloids, even in complex biological fluids.

Original languageEnglish
Pages (from-to)195-199
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume448
Issue number2
DOIs
Publication statusPublished - 30 May 2014

Keywords

  • Aggregation
  • Alzheimer's disease
  • Amyloid beta
  • Fluorescence correlation spectroscopy
  • Oligomerization
  • Protein folding disease

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