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Oxysterols, especially 7-ketocholesterol (7-KC), may amplify AD pathology by increasing neuroinflammation and oxidative damage through mitochondrial dysfunction, lipid peroxidation, and inflammation. The study focuses on sulphated oxysterols, including 7-Ketocholesterol-3-sulfate (7KCS) and (26HC3S), assessing their synthesis and extraction from APOE4 astrocytes and APOE4 knockout controls.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/7-keto-cholesterol-as-a-mediator-in-alzheimers-disease-pathogenesis-poster-presentation/459297/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/7-keto-cholesterol-as-a-mediator-in-alzheimers-disease-pathogenesis-poster-presentation/459297.png","ImageObject",300,407,{"name":92,"@type":93},"Aria","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-08","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does 7-ketocholesterol (7-KC) play in Alzheimer’s disease pathology?","Question",{"text":112,"@type":113},"7-KC may worsen AD pathology by exacerbating neuroinflammatory and oxidative damage, including mitochondrial dysfunction, lipid peroxidation, and inflammation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How were sulphated oxysterols synthesized for the study?",{"text":117,"@type":113},"7-Ketocholesterol-3-sulfate (7KCS) pyridinium salt and (25R)-26-hydroxycholesterol-3-sulfate (26HC3S) sodium salt were synthesized starting from cholesterol and diosgenin, respectively.",{"name":119,"@type":110,"acceptedAnswer":120},"What did the LC-MS/MS results show in APOE4 vs. knockout astrocytes?",{"text":121,"@type":113},"LC-MS/MS quantified 7KCS and 26HC3S and showed significantly elevated sulphated oxysterol levels in APOE4 astrocytes compared to APOE4 knockout controls.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},459297,1790755624,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":8,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":129,"read_time":81,"preview_page_count":4},2336464648322,"https://ap-avatar.wpscdn.com/avatar/2200025388227c56fec?_k=1778556882303663488","DOI: 10. 1002/alz70856_105279  \nBIOMARKERS  \nPOSTER PRESENTATION  \nBIOMARKERS (NON-NEUROIMAGING)  \n7-Keto Cholesterol as a Mediator in Alzheimer’s Disease Pathogenesis  \nIrundika HK Dias1  Lorena Diaz-Sanchez2  Tommaso Angelini3  Maura Marinozzi3  \n1Aston University, Birmingham, West Midlands, United Kingdom  \n2Aston University, Birmingham, United Kingdom  \n3 University of Perugia, Perugia, Perugia, Italy  \nCorrespondence  \nIrundika HK Dias, Aston University, Birmingham, West Midlands, United Kingdom. [Email:](Email: diashki1@aston.ac.uk)[ diashki1@aston.ac.uk](Email: diashki1@aston.ac.uk)  \nAbstract  \nBackground: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation, tau hyperphosphorylation, and oxidative stress. Recent evidence suggests that oxysterols, particularly 7-ketocholesterol (7-KC) may play a pivotal role in AD pathology by exacerbating neuroinflammatory and oxidative damage. 7-KC, a major non-enzymatic oxidation product of cholesterol, is known to contribute to neurotoxicity through mitochondrial dysfunction, lipid peroxidation, and inflammation. Unlike other oxysterols, 7-KCis highly reactive and has been implicated in cell death pathways relevant toneurodegeneration, including ferroptosis and autophagy dysregulation. Sulphation of 7-KC alter its solubility, bioavailability, and interaction with cellular receptors, potentially amplifying its cytotoxic effects in neuronal and glial cells.  \nMethod: 7-Ketocholesterol-3-sulfate (7KCS) pyridinium salt and (25R)-26-hydroxycholesterol-3-sulfate (26HC3S) sodium salt were synthesized starting from cholesterol and diosgenin, respectively. Total sulphated oxysterols were extracted from APOE4 astrocytes and APOE4 knockout astrocytes. Briefly, cell lysates were spiked with internal deuterated standard, 7-KCd5 and oxysterols were enriched using two-step solid phase extraction (SPE) using a polymeric SPE column (HLB PRiME, Waters). A multiple reaction monitoring (MRM) based liquid chromatography-mass spectrometry (LC-MS/MS) method was developed and validated for the absolute quantification of (26HC3S) and 7KCS.  \nResult: The LC-MS/MS analysis successfully quantified 7KCS and 26HC3S in APOE4 astrocytes and APOE4 knockout astrocytes, revealing significantly elevated levels of sulphated oxysterols inAPOE4 astrocytes compared to knockout controls. Conclusion: This data suggest a potential role in cholesterol metabolism dysregulation and neuroinflammation associated with Alzheimer’s disease  \nThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \n© 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association.  \nAlzheimer’s Dement. 2025;21(Suppl. 2):e105279.  \n[https://doi.org/10.1002/alz70856_105279](https://doi.org/10.1002/alz70856_105279)  \nwi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz)  \n1of1","cbCaisVtw6OPCCmM","https://ap.wps.com/l/cbCaisVtw6OPCCmM","pdf",78151,"English","# Biomarkers\n## Poster Presentation\n## Methods\n## Results\n## Conclusion","[{\"question\":\"What role does 7-ketocholesterol (7-KC) play in Alzheimer’s disease pathology?\",\"answer\":\"7-KC may worsen AD pathology by exacerbating neuroinflammatory and oxidative damage, including mitochondrial dysfunction, lipid peroxidation, and inflammation.\"},{\"question\":\"How were sulphated oxysterols synthesized for the study?\",\"answer\":\"7-Ketocholesterol-3-sulfate (7KCS) pyridinium salt and (25R)-26-hydroxycholesterol-3-sulfate (26HC3S) sodium salt were synthesized starting from cholesterol and diosgenin, respectively.\"},{\"question\":\"What did the LC-MS/MS results show in APOE4 vs. knockout astrocytes?\",\"answer\":\"LC-MS/MS quantified 7KCS and 26HC3S and showed significantly elevated sulphated oxysterol levels in APOE4 astrocytes compared to APOE4 knockout controls.\"}]","7-Keto Cholesterol as a Mediator in Alzheimer’s Disease Pathogenesis - Poster Presentation | PDF"]