Plasma exosome proteomics reveals the pathogenesis mechanism of post stroke cognitive impairment

Abstract

Background Recently, the plasma exosome biomarkers of post-stroke cognitive impairment (PSCI) have been brought into focus. Exploration and utilization of exosome biomarkers and their related functions provided the possibility for the diagnosis and treatment of PSCI. Aims To identify for new diagnostic and prognostic biomarkers of plasma exosome using label-free quantitative proteomics and biological information analysis in PSCI patients. Methods A series of behavioral assessments were performed, including the Mini-Mental Status Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Barthel index, the Morse Fall Seale (MFS) beteen control group (n = 10) and PSCI group (n = 10). The blood samples were collected to analyse the biomarker and differentially expressed proteins of plasma exosome using label-free quantitative proteomics and biological information. The exosomes marker proteins were determined by Western blot. The exosome morphology was observed by transmission electron microscopy. Results The scores of MMSE and MoCA were significantly decreasd in the PSCI group. The PT% and high-density lipoprotein decreasd and the INR ratio increasd in PSCI group. The mean size of exosome was approximately 71.6 nm and the concentration was approximately 6.8E + 7 particles/mL. Exosome proteomics identificated 259 differentially expressed proteins, including 131 up-regulated proteins and 128 down-regulated proteins. The mechanisms of cognitive impairment are related to up-regulation of degradation of ubiquitinated proteins, calcium dependent protein binding, cytoskeleton reorganization, platelet aggregation and down-regulation of cell adhesive protein binding, formation of fibrin clot, complement activation, lipid metabolism and ATP-dependent degradation of ubiquitinated proteins in plasma exosome of PSCI patients. Plasma levels of YWHAZ and BAIAP2 were significantly increased while that of IGHD, ABCB6 and HSPD1 were significantly decreased in PSCI patients. Conclusion These proteins might be target-related proteins and provide global insights into pathogenesis mechanisms of PSCI at plasma exosome proteins level.