Abstract
INTRODUCTION
The apolipoprotein E (APOE) ε4 allele exerts a significant influence on peripheral inflammation and neuroinflammation, yet the underlying mechanisms remain elusive.
METHODS
The present study enrolled 54 patients diagnosed with late-onset Alzheimer’s disease (AD; including 28 APOE ε4 carriers and 26 non-carriers). Plasma inflammatory cytokine concentration was assessed, alongside bulk RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq) analysis of peripheral blood mononuclear cells (PBMCs).
RESULTS
Plasma tumor necrosis factor α, interferon γ, and interleukin (IL)-33 levels increased in the APOE ε4 carriers but IL-7 expression notably decreased. A negative correlation was observed between plasma IL-7 level and the hippocampal atrophy degree. Additionally, the expression of IL-7R and CD28 also decreased in PBMCs of APOE ε4 carriers. ScRNA-seq data results indicated that the changes were mainly related to the CD4+ Tem (effector memory) and CD8+ Tem T cells.
DISCUSSION
These findings shed light on the role of the downregulated IL-7/IL-7R pathway associated with the APOE ε4 allele in modulating neuroinflammation and hippocampal atrophy.
Highlights
The apolipoprotein E (APOE) ε4 allele decreases plasma interleukin (IL)-7 and aggravates hippocampal atrophy in Alzheimer’s disease.
Plasma IL-7 level is negatively associated with the degree of hippocampal atrophy.
The expression of IL-7R signaling decreased in peripheral blood mononuclear cells of APOE ε4 carriers
Dysregulation of the IL-7/IL-7R signal pathways enriches T cells.
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This post is Copyright: Ying‐Jie Zhang,
Yan Cheng,
Hai‐Liang Tang,
Qi Yue,
Xin‐Yi Cai,
Zhi‐Jie Lu,
Yi‐Xuan Hao,
An‐Xiang Dai,
Ting Hou,
Hao‐Xin Liu,
Nan Kong,
Xiao‐Yu Ji,
Chang‐Hao Lu,
Sheng‐Liang Xu,
Kai Huang,
Xin Zeng,
Ya‐Qi Wen,
Wan‐Yin Ma,
Ji‐Tian Guan,
Yan Lin,
Wen‐Bin Zheng,
Hui Pan,
Jie Wu,
Ren‐Hua Wu,
Nai‐Li Wei | August 12, 2024