Rapid and selective separation of amyloid beta from its stereoisomeric point mutations implicated in neurodegenerative Alzheimer’s disease

• Published in: Analytica chimica acta 2021-06, Vol.1163, p.338506-338506, Article 338506
• Main Authors: Readel, Elizabeth R., Wey, Michael, Armstrong, Daniel W.
• Format: Article
• Language: English
• Subjects: Amyloid beta epimer; Aspartic acid isomerization; D-Aspartic acid; D-Serine; L/D-iso-Aspartic acid
• ISSN: 0003-2670; 1873-4324
• DOI: 10.1016/j.aca.2021.338506

Extracellular deposition of amyloid beta (Aβ) peptides are a hallmark of Alzheimer’s disease. The isomerization and epimerization of Aβ peptides have been linked to the enhanced deposition of Aβ plaques. Therefore, considerable effort has been expended to create effective methods to distinguish such aberrant Aβ peptides from normal Aβ peptides. Herein, we have developed chromatographic retention U-shaped curves to investigate the hydrophobicity of Aβ 1–38, 1–40, 1–42 and fourteen aberrant Aβ 1–42 peptides. Using this information, we developed the first selective and comprehensive method that can easily detect both aberrant and normal Aβ peptides simultaneously using high performance liquid chromatography-mass spectrometry (HPLC-MS). We show for the first time that D-Ser modifications to Aβ cause the peptide to be more hydrophilic, as does D-Asp and L/D-iso-Asp. [Display omitted] •Rapid detection of aberrant and normal (i.e., all l-amino acids) Aβ 1–38, 1–40, 1–42.•Epimeric Aβ peptides containing: D-Asp, L-iso-Asp, D-iso-Asp, D-Ser are studied.•Epimeric and isomeric Aβ peptides have characteristic chromatographic separations.•Hydrophilicity varies in epimeric Aβ peptides implying variable secondary structure.