Physico-chemical methods for studing β-amyloid aggregation

Abstract

Alzheimer's disease is the most prevalent neurodegenerative pathology. According to the amyloid cascade hypothesis, a key event of the Alzheimer's disease pathogenesis is a transition of the β-amyloid peptide (Aβ) from the monomelic form to the aggregated state. The mechanism of Aβ aggregation is intensively studied in vitro, by means of synthetic peptides and various physico-chemical methods allowing evaluation of size, molecular structure, and morphology of the formed aggregates. The paper reviews both the well-known and recently introduced physico-chemical methods for analysis of Aβ aggregation, including microscopy, optical and fluorescent methods, method of electron paramagnetic resonance, electrochemical and eleclrophoretic methods, gel-filtration, and mass spectrometric methods. Merits and drawbacks of the methods are discussed. The unique possibility to simultaneously observe Aβ monomers as well oligomers and. large aggregates by means of atomic force microscopy or fluorescence correlation spectroscopy is emphasized. The high detection sensitivity of the latter method, monitoring the aggregation process in Aβ solutions at low peptide concentrations is underlined. Among mass spectrometric methods, the ion mobility mass spectrometry is marked out as a method enabling to obtain information about both the spectrum of Aβ oligomers and their structure. It is pointed out that the use of several methods giving the complementary data about Aβ aggregates is the best experimental approach to studying the process of β-amyloid peptide aggregation in vitro.