PNNL

Abstract

Accumulation of ß-amyloid (Aß) is one of the hallmarks of Alzheimer’s disease. The deposition of ß-amyloid plaques is likely to start years in advance of manifestation of clinical symptoms, although the exact timing is unknown. Over the years, Aß peptides undergo post-translational modifications and stereoisomerization. Analysis of stereoisomers is particularly challenging due to their identical elemental composition and similar physicochemical properties. Herein we have utilized our recently developed structures for lossless ion manipulations ion mobility-mass spectrometry platform (SLIM IM-MS), in conjunction with SLIM serpentine ultralong path with extended routing (SUPER), to baseline resolve four distinct sets of Aß17-28 tryptic peptide epimers on a rapid (~1 second) timescale. We discovered that sodium adduct ions, [M+H+Na]2+, allowed baseline IM resolution for all Aß epimer sets assessed, while such baseline separations were unachievable for their [M+2H]2+ doubly protonated ions.