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Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA\u2010seq) and single\u2010cell RNA sequencing (scRNA\u2010seq) analysis of peripheral blood mononuclear cells (PBMCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Plasma tumor necrosis factor \u03b1, interferon \u03b3, and interleukin (IL)\u201033 levels increased in the <jats:italic>APOE<\/jats:italic> \u03b54 carriers but IL\u20107 expression notably decreased. A negative correlation was observed between plasma IL\u20107 level and the hippocampal atrophy degree. Additionally, the expression of IL\u20107R and CD28 also decreased in PBMCs of <jats:italic>APOE<\/jats:italic> \u03b54 carriers. ScRNA\u2010seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>These findings shed light on the role of the downregulated IL\u20107\/IL\u20107R pathway associated with the <jats:italic>APOE<\/jats:italic> \u03b54 allele in modulating neuroinflammation and hippocampal atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The apolipoprotein E (<jats:italic>APOE<\/jats:italic>) \u03b54 allele decreases plasma interleukin (IL)\u20107 and aggravates hippocampal atrophy in Alzheimer's disease.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Plasma IL\u20107 level is negatively associated with the degree of hippocampal atrophy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The expression of IL\u20107R signaling decreased in peripheral blood mononuclear cells of <jats:italic>APOE<\/jats:italic> \u03b54 carriers<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Dysregulation of the IL\u20107\/IL\u20107R signal pathways enriches T cells.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14173","type":"journal-article","created":{"date-parts":[[2024,8,12]],"date-time":"2024-08-12T02:04:34Z","timestamp":1723428274000},"page":"6441-6455","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["<i>APOE<\/i> \u03b54\u2013associated downregulation of the IL\u20107\/IL\u20107R pathway in effector memory T cells: Implications for Alzheimer's disease"],"prefix":"10.1002","volume":"20","author":[{"given":"Ying\u2010Jie","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Shantou University Medical College  Shantou China"},{"name":"Department of Rehabilitation The First 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