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.

中文翻译：

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阿尔茨海默病中各种β-淀粉样蛋白的质谱研究

本综述涵盖了应用质谱 (MS) 技术研究人体样本中 β-淀粉样蛋白 (Aβ) 肽的多样性的结果。由于 Aβ 是阿尔茨海默病 (AD) 的重要标志，阿尔茨海默病是全球老年人的一种具有社会意义的神经退行性疾病，因此分析其内源性变异对于阐明 AD 的发病机制、预测疾病发病风险的增加以及开发有效的疗法。MS 方法对于复杂样品的研究没有其他选择，包括各种长度和修饰不同的 Aβ 蛋白形式。基于基质辅助激光解吸/电离飞行时间和电喷雾电离串联 MS 液相色谱的方法在 Aβ 研究中最为常见。然而，具有异构化和/或外消旋 Asp 和 Ser 残基的 Aβ 形式需要使用特殊的分离方法和超灵敏和选择性的检测方法。总的来说，这篇综述总结了目前在人脑、脑脊液和血浆中发现的 Aβ 物种的知识；侧重于不同 MS 方法在 Aβ 研究中的应用；并考虑了 MS 技术在 Aβ 肽进一步研究中的潜力。