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

Abstract

Exploration and utilization of exosome biomarkers and their related functions provide the possibility for the diagnosis and treatment of post-stroke cognitive impairment (PSCI). To identify the new diagnostic and prognostic biomarkers of plasma exosome were uzed label-free quantitative proteomics and biological information analysis in PSCI patients. Behavioral assessments were performed, including the Mini-Mental Status Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Barthel index, the Morse Fall Seale (MFS) between 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. The scores of MMSE and MoCA were significantly decreased in the PSCI group. The PT% and high-density lipoprotein decreased and the INR ratio increased 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 identified 259 differentially expressed proteins. The mechanisms of cognitive impairment are related to regulate the degradation of ubiquitinated proteins, calcium dependent protein binding, cell adhesive protein binding, formation of fibrin clot, 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. These proteins might be target-related proteins and provide global insights into pathogenesis mechanisms of PSCI at plasma exosome proteins level.

Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis

“…YWHAZ, part of the 14–3–3 protein family, affects cellular proliferation, migration, and differentiation by interacting with phosphoserine- and serine-containing proteins . Clinically, elevated levels of YWHAZ poststroke have been associated with cognitive impairment, while experimental models demonstrate that reduced YWHAZ expression leads to neurodevelopmental and cognitive deficits . Our study establishes the significance of five proteins in ischemic stroke, highlighting their potential as biomarkers and therapeutic targets.…”

Post-stroke cognitive impairment: exploring molecular mechanisms and omics biomarkers for early identification and intervention

“…According to Qi et al (2023) , 31 proteins that were up-regulated in PSCI patients compared to controls may be connected to platelet aggregation and coagulation, whereas 128 proteins that were down-regulated may be connected to pathways such complement activation, fibrin clotting, and cell adhesion protein binding. However, a quantitative proteomics study of plasma in patients with lacunar infarction identified 112 proteins associated with cognitive decline ( Datta et al, 2022 ), most of which were not associated with inflammation, complement activation, coagulation, fibrinolysis, or endothelium.…”

Comprehensive Assessment of Ischemic Stroke in Nonhuman Primates: Neuroimaging, Behavioral, and Serum Proteomic Analysis

“…YWHAZ, part of the 14-3-3 protein family, affects cellular proliferation, migration, and differentiation by interacting with phosphoserine-and serine-containing proteins (Aghazadeh & Papadopoulos, 2016). Clinically, elevated levels of YWHAZ post-stroke have been associated with cognitive impairment (Qi et al, 2023), while experimental models demonstrate that reduced YWHAZ expression leads to neurodevelopmental and cognitive deficits (Wan et al, 2023). Our study establishes the significance of five proteins in in ischemic stroke, highlighting their potential as biomarkers and therapeutic targets.…”