Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, 76019, USA.
Sci Rep. 2023 Jul 31;13(1):12387. doi: 10.1038/s41598-023-38788-1.
Extracellular deposition of amyloid beta (Aβ) peptide is a contributing factor of Alzheimer's disease (AD). Considerable effort has been expended to create effective antibodies, or immunotherapies, targeting Aβ peptides. A few immunotherapies are thought to provide some benefit. It is possible that a contributing factor to the responses of such therapies may be the presence of modified, or aberrant, Aβ peptides found in AD patients. These aberrations include the isomerization and epimerization of L-Asp and L-Ser residues to form D-Asp, L/D-isoAsp, and D-Ser residues, respectively. An effective methodology is essential to isolate all Aβ peptides and then to quantify and locate the aberrant amino acids. Modifications to Aβ peptides may elevate the deposition of Aβ plaques and/or contribute to the neurodegeneration in AD patients, and may alter the binding affinity to antibodies. Herein, we used immunoprecipitation to examine the binding affinity of four antibodies against 18 epimeric and/or isomeric Aβ peptides compared to wild type (all L) Aβ peptide. Tandem mass spectrometry was used as a detection method, which also was found to produce highly variable results for epimeric and/or isomeric Aβ.
细胞外淀粉样蛋白β（Aβ）肽的沉积是阿尔茨海默病（AD）的一个致病因素。人们花费了大量精力来开发针对 Aβ 肽的有效抗体或免疫疗法。一些免疫疗法被认为具有一定的益处。这些疗法之所以有反应，其原因之一可能是 AD 患者中存在修饰的或异常的 Aβ 肽。这些异常包括 L-Asp 和 L-Ser 残基分别异构化为 D-Asp、L/D-异天冬氨酸和 D-Ser 残基。因此，建立一种有效的方法来分离所有 Aβ 肽并定量和定位异常氨基酸是至关重要的。Aβ 肽的修饰可能会增加 Aβ 斑块的沉积，/或导致 AD 患者的神经退行性变，并可能改变与抗体的结合亲和力。在此，我们使用免疫沉淀法比较了四种针对 18 个异构和/或异构 Aβ 肽的抗体与野生型（均为 L）Aβ 肽的结合亲和力。串联质谱法被用作检测方法，但对于异构和/或异构 Aβ 肽，它也会产生高度可变的结果。
