Quantitative Measurement of Intact Alpha-Synuclein Proteoforms from Post-Mortem Control and Parkinson's Disease Brain Tissue by Intact Protein Mass Spectrometry

摘要: A robust top down proteomics method is presented for profiling alpha-synuclein species from autopsied human frontal cortex brain tissue Parkinson's cases and controls. The was used to test the hypothesis that pathology associated will have a different profile of post-translationally modified than control samples. Validation sample processing steps, mass spectrometry based measurements, data steps were performed. intact protein quantitation features extraction integration m/z each charge state detected fitting simple linear model which accounts concentration variability. validated with serial dilutions standards. Using on samples, several previously unreported modifications in identified. Low levels phosphorylated alpha synuclein fractions enriched Lewy body marginally significant between PD controls (p = 0.03).