Physico-chemical methods for studying amyloid-β aggregation

• Published in: Biochemistry (Moscow). Supplement. Series B, Biomedical chemistry Vol. 9; no. 3; pp. 258 - 274
• Main Authors: Radko, S. P., Khmeleva, S. A., Suprun, E. V., Kozin, S. A., Bodoev, N. V., Makarov, A. A., Archakov, A. I., Shumyantseva, V. V.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.07.2015
• Subjects: Bioorganic Chemistry; Chemistry; Chemistry and Materials Science; Medicinal Chemistry; amyloid-β; aggregation; Alzheimer’s disease; analytical methods
• ISSN: 1990-7508; 1990-7516
• DOI: 10.1134/S1990750815030075

Alzheimer’s disease is the most prevalent neurodegenerative pathology. According to the amyloid cascade hypothesis, transition of the amyloid-β peptide (Aβ) from the monomeric form to the aggregated state is a key event in pathogenesis of the Alzheimer’s disease. 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 review considers both the wellknown and recently introduced physico-chemical methods for analysis of Aβ aggregation, including microscopy, optical and fluorescent methods, electron paramagnetic resonance, electrochemical and electrophoretic methods, gel-filtration, and mass spectrometric methods. Advantages and disadvantages of these methods are considered. Special attention is paid to the unique possibility of simultaneous analysis of both Aβ monomers and its oligomers as well as large aggregates by means of atomic force microscopy or fluorescence correlation spectroscopy. The high detection sensitivity of the latter method provides opportunity for investigating the aggregation process in Aβ solutions of low peptide concentrations. Among mass spectrometric methods, the ion mobility mass spectrometry is considered as a method enabling to obtain information about both the spectrum of Aβ oligomers and their structure. Simultaneous employment of several methods providing complementary data about Aβ aggregates is the best experimental approach for studying the process of Aβ aggregation in vitro.