Complete identification of all 20 relevant epimeric peptides in β-amyloid: a new HPLC-MS based analytical strategy for Alzheimer's research
Siqi Du, Elizabeth R. Readel, Michael Wey, Daniel W. Armstrong
Abstract
Although the underlying cause of Alzheimer's disease (AD) is not known, the extracellular deposition of β-amyloid (Aβ) is considered as a hallmark of AD brains. Evidence has shown the occurrence of d-Asp, isoAsp, and d-Ser residues in Aβ, which may be indicative of and/or contribute to the neurodegeneration in AD patients. Herein, we have developed the first high-throughput profiling technique for all 20 isobaric Aβ peptide epimers containing Asp, isoAsp, and Ser isomers using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). This new analytical strategy allows the direct detection and identification of all possible Asp, isoAsp, and Ser stereoisomers in Aβ, and may contribute to a better understanding of the pathogenesis of AD.