Complete identification of all 20 relevant epimeric peptides in β-amyloid: a new HPLC-MS based analytical strategy for Alzheimer's research

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.