Characterization of amyloid ß peptides in cerebrospinal fluid by an automated immunoprecipitation procedure followed by mass spectrometry
Characterization of amyloid ß peptides in cerebrospinal fluid by an automated immunoprecipitation procedure followed by mass spectrometry
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DOI：
10.1021/pr0703627
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发表时间：
2007-11-01
影响因子：
4.4
通讯作者：
Westman-Brinkmalm, Ann
中科院分区：
文献类型：
--
作者：
Portelius, Erik;Tran, Ai Jun;Westman-Brinkmalm, Ann
阿尔茨海默病的致病事件被认为与β -淀粉样肽（A β 1-42）的神经毒性42氨基酸形式的产生和清除之间的不平衡有关。尽管人们对A β 1-42的产生了解很多，但关于它的降解仍然存在许多问题。在这里，我们描述了一种优化的自动免疫沉淀质谱法，可以准确快速地监测脑脊液中的主要A β亚型。此外，我们描述了一种技术的抗体固定化，最大限度地减少背景信号。利用基质辅助激光解吸/电离飞行时间质谱、纳米流液相色谱和混合线性阱傅立叶变换离子回旋共振质谱串联质谱对这些A β产物进行了鉴定。最后，我们报告了两个新的A β肽（A β 2-17和A β 3-17）的发现。
Pathogenic events in Alzheimer's disease are believed to involve an imbalance between the production and clearance of the neurotoxic 42 amino acid form of the beta-amyloid peptide (A beta 1-42). Although much is known about the production of A beta 1-42, many questions remain about its degradation. Here, we describe an optimized automated immunoprecipitation mass spectrometry method that enables accurate and rapid monitoring of the major A beta isoforms in cerebrospinal fluid. Furthermore, we describe a technique of antibody immobilization, minimizing background signals. The identities of these A beta products were confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nanoflow liquid chromatography and tandem mass spectrometry with a hybrid linear trap Fourier transform ion cyclotron resonance mass spectrometer. Finally, we report the finding of two novel A beta peptides (A beta 2-17 and A beta 3-17).