{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T21:54:14Z","timestamp":1794002054793,"version":"4.8.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515220230 , 2022A1515220001"],"award-info":[{"award-number":["2023A1515220230 , 2022A1515220001"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The identification of plasma biomarkers for the diagnosis of Alzheimer\u2019s disease (AD) has been a longstanding research priority; however, few plasma biomarkers have yet been implemented in routine clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study enrolled 141 participants, including 71 patients with AD, 44 individuals with mild cognitive impairment, and 28 cognitively healthy controls (HC). A total of 16 plasma inflammatory proteins were quantified using multiplex liquid-chip assays, and APOE genotyping was performed. The diagnostic utility of plasma proteins was assessed using the least absolute shrinkage and selection operator (LASSO) with nested cross-validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with AD exhibited marked alterations in plasma inflammatory profiles, with elevated levels of IFN-\u03b3, IL-33, and IL-18, and reduced levels of IL-7 and CCL11. Integrating inflammatory markers with clinical variables and APOE genotype substantially improved discrimination between AD and HC, increasing the area under the ROC curve from 0.863 to 0.953. Among all biomarkers, IFN-\u03b3 emerged as the most informative predictor and was significantly elevated in AD patients carrying the APOE \u03f54 allele. Analyses of single-nucleus RNA sequencing data further revealed pronounced enrichment of IFN-\u03b3 signaling in APOE4\/4 AD-associated lipid droplet-accumulating microglia (LDAM), defined by high ACSL1 expression. Notably, IFN-\u03b3 stimulation enhanced ACSL1 expression in ApoE4-overexpressing HMC3 microglial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings provide a new perspective on the involvement of plasma inflammatory markers for AD diagnosis, and suggest a novel link between IFN-\u03b3 and APOE \u03f54-associated AD risk through modulating the ACSL1-driven pathogenic LDAM phenotype.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1770509","type":"journal-article","created":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:18:25Z","timestamp":1771305505000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Identification of plasma inflammatory biomarkers for Alzheimer\u2019s disease reveals IFN-\u03b3 as a regulator of ACSL1-mediated microglia phenotype"],"prefix":"10.3389","volume":"17","author":[{"given":"Ronghua","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]},{"name":"Laboratory of Molecular Cardiology, The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]},{"name":"Department of Anesthesiology, The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing-Biao","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Cancer Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijie","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]},{"name":"Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixuan","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenrui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Rongcheng Women Infant Health Care Hospital","place":["Jieyang, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation, The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naili","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shantou University Medical College","place":["Shantou, Guangdong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shantou 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