Huriye Ercan, Christina Maria Reumiller, Jacqueline Mühlberger, Felicia Hsu, Georg Johannes Schmidt, Ellen Umlauf, Ingrid Miller, Eduard Rappold, Johannes Attems, Rudolf Oehler, Maria Zellner
{"title":"血小板反映了阿尔茨海默病中额叶抗氧化系统的变化","authors":"Huriye Ercan, Christina Maria Reumiller, Jacqueline Mühlberger, Felicia Hsu, Georg Johannes Schmidt, Ellen Umlauf, Ingrid Miller, Eduard Rappold, Johannes Attems, Rudolf Oehler, Maria Zellner","doi":"10.1002/alz.70117","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>Blood biomarkers reflecting Alzheimer's disease (AD) pathophysiology can improve diagnosis and treatment.</p>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>We applied top-down proteomics to compare frontal lobe from 17 AD cases and 11 controls to blood platelets from a second independent study group of 124 AD patients, 61 with mild cognitive impairment (MCI), and 168 controls. Findings were immunologically validated.</p>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>Sixty AD-associated proteoforms were identified in frontal lobe, with 26 identically represented in platelets. Validation in platelet samples confirmed elevated glutathione S-transferase omega 1 (GSTO1) levels linked to single nucleotide polymorphism (SNP) rs4925 and increased superoxide dismutase 1 (SOD1) levels in AD. Bioinformatics revealed copper chaperone for superoxide dismutase (CCS) and glutathione peroxidase 1 (GPX1) as integral partners of these antioxidant enzymes. Both were detected to be reduced in frontal lobes and platelets in AD. SOD1 and CCS are already changed in MCI.</p>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>These four novel blood biomarkers, integrated with traditional AD biomarkers, may facilitate patient risk assessment and treatment, with SOD1 and CCS alterations in MCI offering early diagnostic potential.</p>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Platelets mirror several Alzheimer's disease (AD)–dependent neuronal changes, valuable for blood tests.</li>\n \n <li>As a start, 60 AD-associated frontal lobe proteins were identified by top-down proteomics.</li>\n \n <li>Fifty percent of these 60 AD-affected brain proteins are represented identically in platelets.</li>\n \n <li>Among these, glutathione S-transferase omega 1 (GSTO1), superoxide dismutase 1 (SOD1), copper chaperone for superoxide dismutase (CCS), and glutathione peroxidase 1 (GPX1) are identically AD related in brain and platelets.</li>\n \n <li>SOD1 and its crucial activating partner CCS are altered in the platelets of patients with mild cognitive impairment.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 4","pages":""},"PeriodicalIF":13.0000,"publicationDate":"2025-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70117","citationCount":"0","resultStr":"{\"title\":\"Platelets mirror changes in the frontal lobe antioxidant system in Alzheimer's disease\",\"authors\":\"Huriye Ercan, Christina Maria Reumiller, Jacqueline Mühlberger, Felicia Hsu, Georg Johannes Schmidt, Ellen Umlauf, Ingrid Miller, Eduard Rappold, Johannes Attems, Rudolf Oehler, Maria Zellner\",\"doi\":\"10.1002/alz.70117\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>Blood biomarkers reflecting Alzheimer's disease (AD) pathophysiology can improve diagnosis and treatment.</p>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>We applied top-down proteomics to compare frontal lobe from 17 AD cases and 11 controls to blood platelets from a second independent study group of 124 AD patients, 61 with mild cognitive impairment (MCI), and 168 controls. Findings were immunologically validated.</p>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>Sixty AD-associated proteoforms were identified in frontal lobe, with 26 identically represented in platelets. Validation in platelet samples confirmed elevated glutathione S-transferase omega 1 (GSTO1) levels linked to single nucleotide polymorphism (SNP) rs4925 and increased superoxide dismutase 1 (SOD1) levels in AD. Bioinformatics revealed copper chaperone for superoxide dismutase (CCS) and glutathione peroxidase 1 (GPX1) as integral partners of these antioxidant enzymes. Both were detected to be reduced in frontal lobes and platelets in AD. SOD1 and CCS are already changed in MCI.</p>\\n </section>\\n \\n <section>\\n \\n <h3> DISCUSSION</h3>\\n \\n <p>These four novel blood biomarkers, integrated with traditional AD biomarkers, may facilitate patient risk assessment and treatment, with SOD1 and CCS alterations in MCI offering early diagnostic potential.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Highlights</h3>\\n \\n <div>\\n <ul>\\n \\n <li>Platelets mirror several Alzheimer's disease (AD)–dependent neuronal changes, valuable for blood tests.</li>\\n \\n <li>As a start, 60 AD-associated frontal lobe proteins were identified by top-down proteomics.</li>\\n \\n <li>Fifty percent of these 60 AD-affected brain proteins are represented identically in platelets.</li>\\n \\n <li>Among these, glutathione S-transferase omega 1 (GSTO1), superoxide dismutase 1 (SOD1), copper chaperone for superoxide dismutase (CCS), and glutathione peroxidase 1 (GPX1) are identically AD related in brain and platelets.</li>\\n \\n <li>SOD1 and its crucial activating partner CCS are altered in the platelets of patients with mild cognitive impairment.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":7471,\"journal\":{\"name\":\"Alzheimer's & Dementia\",\"volume\":\"21 4\",\"pages\":\"\"},\"PeriodicalIF\":13.0000,\"publicationDate\":\"2025-04-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70117\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer's & Dementia\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/alz.70117\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer's & Dementia","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/alz.70117","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Platelets mirror changes in the frontal lobe antioxidant system in Alzheimer's disease
INTRODUCTION
Blood biomarkers reflecting Alzheimer's disease (AD) pathophysiology can improve diagnosis and treatment.
METHODS
We applied top-down proteomics to compare frontal lobe from 17 AD cases and 11 controls to blood platelets from a second independent study group of 124 AD patients, 61 with mild cognitive impairment (MCI), and 168 controls. Findings were immunologically validated.
RESULTS
Sixty AD-associated proteoforms were identified in frontal lobe, with 26 identically represented in platelets. Validation in platelet samples confirmed elevated glutathione S-transferase omega 1 (GSTO1) levels linked to single nucleotide polymorphism (SNP) rs4925 and increased superoxide dismutase 1 (SOD1) levels in AD. Bioinformatics revealed copper chaperone for superoxide dismutase (CCS) and glutathione peroxidase 1 (GPX1) as integral partners of these antioxidant enzymes. Both were detected to be reduced in frontal lobes and platelets in AD. SOD1 and CCS are already changed in MCI.
DISCUSSION
These four novel blood biomarkers, integrated with traditional AD biomarkers, may facilitate patient risk assessment and treatment, with SOD1 and CCS alterations in MCI offering early diagnostic potential.
Highlights
Platelets mirror several Alzheimer's disease (AD)–dependent neuronal changes, valuable for blood tests.
As a start, 60 AD-associated frontal lobe proteins were identified by top-down proteomics.
Fifty percent of these 60 AD-affected brain proteins are represented identically in platelets.
Among these, glutathione S-transferase omega 1 (GSTO1), superoxide dismutase 1 (SOD1), copper chaperone for superoxide dismutase (CCS), and glutathione peroxidase 1 (GPX1) are identically AD related in brain and platelets.
SOD1 and its crucial activating partner CCS are altered in the platelets of patients with mild cognitive impairment.
期刊介绍：
Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
