Identification of aspartic and isoaspartic acid residues in amyloid beta peptides, including Abeta1-42, using electron-ion reactions.
Amyloid beta peptides are the major components of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease (AD). Although it is still unclear what initiates the disease, isomerization of aspartic acid residues in Abeta peptides is directly related to the pathology of AD. The detection of isomerization products is analytically challenging, due to their similar chemical properties and identical molecular mass. Different methods have been applied to differentiate and quantify the isomers, including immunology, chromatography, and mass spectrometry. Typically, those methods require comparative analysis with the standard peptides and involve many sample preparation steps. To understand the role of Abeta isomerization in AD progression, a fast, simple, accurate, and reproducible method is necessary. In this work, electron capture dissociation (ECD) Fourier-transform ion cyclotron resonance mass spectrometry (FTICR MS) was applied to detect isomerization in Abeta peptides. ECD generated diagnostic fragment ions for the two isomers of Abeta17-28, [M + 2H - 60]+* and z6*-44 when aspartic acid was present and z6*-57 when isoaspartic acid was present. Additionally, the z(n)-57 diagnostic ion was also observed in the electron ionization dissociation (EID) spectra of the modified Abeta17-28 fragment. ECD was further applied toward Abeta1-40 and Abeta1-42. The diagnostic ion c6 + 57 was observed in the ECD spectra of the Abeta1-42 peptide, demonstrating isomerization at residue 7. In conclusion, both ECD and EID can clearly determine the presence and the position of isoaspartic acid residues in amyloid beta peptides. The next step, therefore, is to apply this method to analyze samples of Alzheimer's patients and healthy individuals in order to generate a better understanding of the disease.
Sargaeva
Nadezda P
NP
Mass Spectrometry Resource, Department of Biochemistry, Boston University School of Medicine, 670 Albany Street, R504, Boston, Massachusetts 02118, USA.
Lin
Cheng
C
O'Connor
Peter B
PB
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D053000:Analytic Sample Preparation Methods; D001224:Aspartic Acid / Q000032:analysis* / Q000737:chemistry; D004583:Electrons; D005583:Fourier Analysis; D057927:Hydrophobic and Hydrophilic Interactions; D026581:Isoaspartic Acid / Q000032:analysis* / Q000737:chemistry; D007536:Isomerism; D013058:Mass Spectrometry; D010446:Peptide Fragments / Q000737:chemistry*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D026581:Isoaspartic Acid; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D001224:Aspartic Acid