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We also assessed biomarkers of AD pathology (A\u03b242, p\u2010tau181, t\u2010tau) and neurodegeneration (neurofilament light\u2010chain [NfL]).<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n Compared to controls, SCRN1 and MMP10 were increased in LOAD and YOAD, but 16 markers showed YOAD\u2010specific increases. Forty\u2010six markers were significantly associated with NfL. P\u2010tau181 and t\u2010tau mediated the association between inflammatory markers and NfL in YOAD. In LOAD we could not identify a direct or indirect relationship between neuroinflammation and neurodegeneration.<\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n Using a proteomics approach, we observed an exacerbation of neuroinflammatory changes and a differential contribution of neuroinflammation to AD pathology and neurodegeneration in YOAD compared to LOAD.<\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Olink's Proximity Extension Assay was used to compare the inflammatory profile of 26 healthy controls and 90 Alzheimer's disease (AD) patients.<\/jats:p>\n <\/jats:list-item>\n \n \n AD patients were further stratified into young\u2010onset (YOAD,\n n<\/jats:italic>\n \u00a0=\u00a057) and late\u2010onset (LOAD,\n n<\/jats:italic>\n \u00a0=\u00a033) AD.\n <\/jats:p>\n <\/jats:list-item>\n \n Cerebrospinal fluid (CSF) levels of MMP10 and SCRN1 were increased in both YOAD and LOAD, but 16 proteins were only increased in YOAD.<\/jats:p>\n <\/jats:list-item>\n \n Tau mediated the association between inflammatory markers and neurodegeneration in YOAD.<\/jats:p>\n <\/jats:list-item>\n \n Neuroinflammation may be differentially involved in the pathogenesis of YOAD compared to LOAD.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70509","type":"journal-article","created":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T09:10:02Z","timestamp":1753434602000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Distinct inflammatory profiles in young\u2010onset versus late\u2010onset Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Simrika","family":"Thapa","sequence":"first","affiliation":[{"name":"Tanz Centre for Research on Neurodegenerative Diseases University of Toronto Toronto Ontario Canada"},{"name":"University Health Network (UHN) Memory Clinic Krembil Brain Institute Toronto Ontario 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