Mass spectrometric studies of the variety of beta‐amyloid proteoforms in Alzheimer's disease

• Published in: Mass spectrometry reviews 2025-01, Vol.44 (1), p.3-21
• Main Authors: Zakharova, Natalia V., Kononikhin, Alexey S., Indeykina, Maria I., Bugrova, Anna E., Strelnikova, Polina, Pekov, Stanislav, Kozin, Sergey A., Popov, Igor A., Mitkevich, Vladimir, Makarov, Alexander A., Nikolaev, Evgeny N.
• Format: Article
• Language: English
• Subjects: Alzheimer Disease - blood; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Alzheimer's disease (AD); Amyloid beta-Peptides - analysis; Amyloid beta-Peptides - cerebrospinal fluid; Amyloid beta-Peptides - metabolism; Aβ peptides; beta‐amyloid; Brain - metabolism; Brain - pathology; Cerebrospinal fluid; Chromatography, Liquid - methods; Humans; IMS; Ionization; isoforms; LC‐MS; Liquid chromatography; MALDI‐TOF; mass spectrometry (MS); Mass Spectrometry - methods; Neurodegenerative diseases; Peptides; post‐translational modifications (PTMs); proteoforms; Spectrometry, Mass, Electrospray Ionization - methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Tandem Mass Spectrometry - methods; β-Amyloid
• ISSN: 0277-7037; 1098-2787
• DOI: 10.1002/mas.21775

This review covers the results of the application of mass spectrometric (MS) techniques to study the diversity of beta‐amyloid (Aβ) peptides in human samples. Since Aβ is an important hallmark of Alzheimer's disease (AD), which is a socially significant neurodegenerative disorder of the elderly worldwide, analysis of its endogenous variations is of particular importance for elucidating the pathogenesis of AD, predicting increased risks of the disease onset, and developing effective therapy. MS approaches have no alternative for the study of complex samples, including a wide variety of Aβ proteoforms, differing in length and modifications. Approaches based on matrix‐assisted laser desorption/ionization time‐of‐flight and liquid chromatography with electrospray ionization tandem MS are most common in Aβ studies. However, Aβ forms with isomerized and/or racemized Asp and Ser residues require the use of special methods for separation and extra sensitive and selective methods for detection. Overall, this review summarizes current knowledge of Aβ species found in human brain, cerebrospinal fluid, and blood plasma; focuses on application of different MS approaches for Aβ studies; and considers the potential of MS techniques for further studies of Aβ‐peptides.