Yidan Zhang , Yuan Zhao , Jian Zhang , Ya Gao , Xuan Gao , Shuyue Li , Cui Chang , Guofeng Yang
{"title":"血浆源性细胞外囊泡的蛋白质组学发现 S100A8 是阿尔茨海默病的新型生物标记物：初步研究","authors":"Yidan Zhang , Yuan Zhao , Jian Zhang , Ya Gao , Xuan Gao , Shuyue Li , Cui Chang , Guofeng Yang","doi":"10.1016/j.jprot.2024.105279","DOIUrl":null,"url":null,"abstract":"<div><p>Extracellular vesicles (EVs) act as mediators for intercellular transfer of Aβ and tau proteins, promoting the propagation of these pathological misfolded proteins throughout the brain in Alzheimer's disease (AD). Levels of blood exosomal Aβ<sub>42</sub>, total Tau (t-Tau) and phosphorylated Tau (p-Tau) had a high correlation with their concentrations in cerebrospinal fluid (CSF), demonstrating that exosomal biomarkers have equal contribution as those in CSF for the diagnosis of AD. We aimed to comprehensively characterize the proteome of plasma-derived EVs to identify differentially expressed proteins (DEPs) and pathways in AD. Tandem mass tag (TMT) labeled quantitative proteomics was applied to analyze plasma-derived EV proteins in 9 AD patients and 9 healthy controls. 335 proteins were quantified, and 12 DEPs were identified including seven upregulated proteins and five down-regulated proteins. Oligomerized Aβ<sub>1–42</sub> induced SH-SY5Y cell damage model was built to mimic the pathological changes of AD, and small interfering RNA (siRNA) against S100A8 was used to knock down S100A8 expression. Results displayed S100A8 was down regulated in plasma-derived EVs from AD patients, while enriched in EVs derived from Aβ<sub>1–42</sub>-induced SH-SY5Y cells. Furthermore, Aβ<sub>1–42</sub>-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aβ levels in cell lysate and EVs, especially in EVs.</p></div><div><h3>Significance</h3><p>The investigation aimed to comprehensively characterize the proteome of plasma-derived EVs to identify DEPs and potential biomarker of AD. S100A8 was found down regulated in plasma-derived EVs from AD patients using TMT labeled quantitative proteomics. The diagnostic value of S100A8 was also confirmed using receiver operating characteristic curve (ROC) analysis. Furthermore, Aβ<sub>1–42</sub>-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aβ levels in cell lysate and EVs, especially in EVs. The preliminary findings suggest that suppression of S100A8 expression inhibits Aβ aggregation both in cell lysate and EVs from Aβ<sub>1–42</sub>-induced SH-SY5Y cells, and S100A8 more likely regulates Aβ aggregation via EVs. Therefore, plasma-derived EV S100A8 might be a potential biomarker of AD. Manipulation of S100A8 expression may be a novel therapeutic strategy in the treatment of AD.</p></div>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Proteomics of plasma-derived extracellular vesicles reveals S100A8 as a novel biomarker for Alzheimer's disease: A preliminary study\",\"authors\":\"Yidan Zhang , Yuan Zhao , Jian Zhang , Ya Gao , Xuan Gao , Shuyue Li , Cui Chang , Guofeng Yang\",\"doi\":\"10.1016/j.jprot.2024.105279\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Extracellular vesicles (EVs) act as mediators for intercellular transfer of Aβ and tau proteins, promoting the propagation of these pathological misfolded proteins throughout the brain in Alzheimer's disease (AD). Levels of blood exosomal Aβ<sub>42</sub>, total Tau (t-Tau) and phosphorylated Tau (p-Tau) had a high correlation with their concentrations in cerebrospinal fluid (CSF), demonstrating that exosomal biomarkers have equal contribution as those in CSF for the diagnosis of AD. We aimed to comprehensively characterize the proteome of plasma-derived EVs to identify differentially expressed proteins (DEPs) and pathways in AD. Tandem mass tag (TMT) labeled quantitative proteomics was applied to analyze plasma-derived EV proteins in 9 AD patients and 9 healthy controls. 335 proteins were quantified, and 12 DEPs were identified including seven upregulated proteins and five down-regulated proteins. Oligomerized Aβ<sub>1–42</sub> induced SH-SY5Y cell damage model was built to mimic the pathological changes of AD, and small interfering RNA (siRNA) against S100A8 was used to knock down S100A8 expression. Results displayed S100A8 was down regulated in plasma-derived EVs from AD patients, while enriched in EVs derived from Aβ<sub>1–42</sub>-induced SH-SY5Y cells. Furthermore, Aβ<sub>1–42</sub>-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aβ levels in cell lysate and EVs, especially in EVs.</p></div><div><h3>Significance</h3><p>The investigation aimed to comprehensively characterize the proteome of plasma-derived EVs to identify DEPs and potential biomarker of AD. S100A8 was found down regulated in plasma-derived EVs from AD patients using TMT labeled quantitative proteomics. The diagnostic value of S100A8 was also confirmed using receiver operating characteristic curve (ROC) analysis. Furthermore, Aβ<sub>1–42</sub>-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aβ levels in cell lysate and EVs, especially in EVs. The preliminary findings suggest that suppression of S100A8 expression inhibits Aβ aggregation both in cell lysate and EVs from Aβ<sub>1–42</sub>-induced SH-SY5Y cells, and S100A8 more likely regulates Aβ aggregation via EVs. Therefore, plasma-derived EV S100A8 might be a potential biomarker of AD. Manipulation of S100A8 expression may be a novel therapeutic strategy in the treatment of AD.</p></div>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-08-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1874391924002112\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1874391924002112","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Proteomics of plasma-derived extracellular vesicles reveals S100A8 as a novel biomarker for Alzheimer's disease: A preliminary study
Extracellular vesicles (EVs) act as mediators for intercellular transfer of Aβ and tau proteins, promoting the propagation of these pathological misfolded proteins throughout the brain in Alzheimer's disease (AD). Levels of blood exosomal Aβ42, total Tau (t-Tau) and phosphorylated Tau (p-Tau) had a high correlation with their concentrations in cerebrospinal fluid (CSF), demonstrating that exosomal biomarkers have equal contribution as those in CSF for the diagnosis of AD. We aimed to comprehensively characterize the proteome of plasma-derived EVs to identify differentially expressed proteins (DEPs) and pathways in AD. Tandem mass tag (TMT) labeled quantitative proteomics was applied to analyze plasma-derived EV proteins in 9 AD patients and 9 healthy controls. 335 proteins were quantified, and 12 DEPs were identified including seven upregulated proteins and five down-regulated proteins. Oligomerized Aβ1–42 induced SH-SY5Y cell damage model was built to mimic the pathological changes of AD, and small interfering RNA (siRNA) against S100A8 was used to knock down S100A8 expression. Results displayed S100A8 was down regulated in plasma-derived EVs from AD patients, while enriched in EVs derived from Aβ1–42-induced SH-SY5Y cells. Furthermore, Aβ1–42-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aβ levels in cell lysate and EVs, especially in EVs.
Significance
The investigation aimed to comprehensively characterize the proteome of plasma-derived EVs to identify DEPs and potential biomarker of AD. S100A8 was found down regulated in plasma-derived EVs from AD patients using TMT labeled quantitative proteomics. The diagnostic value of S100A8 was also confirmed using receiver operating characteristic curve (ROC) analysis. Furthermore, Aβ1–42-induced SH-SY5Y cells treated with S100A8 siRNA showed decreased Aβ levels in cell lysate and EVs, especially in EVs. The preliminary findings suggest that suppression of S100A8 expression inhibits Aβ aggregation both in cell lysate and EVs from Aβ1–42-induced SH-SY5Y cells, and S100A8 more likely regulates Aβ aggregation via EVs. Therefore, plasma-derived EV S100A8 might be a potential biomarker of AD. Manipulation of S100A8 expression may be a novel therapeutic strategy in the treatment of AD.
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