College of Information Engineering, Shanghai Maritime University, Shanghai, 201306, People's Republic of China.
J Mol Neurosci. 2021 Jul;71(7):1485-1494. doi: 10.1007/s12031-021-01809-7. Epub 2021 Mar 9.
Neuroinflammation-induced neurodegeneration and immune cell infiltration are two features of Alzheimer disease (AD). This study aimed to identify potential peripheral biomarkers that interact with cerebrospinal fluid (CSF) and infiltrating immune cells in AD. Blood and CSF data were downloaded from the Alzheimer's disease Neuroimaging Initiative database. We identified differentially expressed genes (DEGs) in AD and assessed infiltrating immune cells using the Immune Cell Abundance Identifier (ImmuCellAI) algorithm. Blood-brain barrier (BBB) and immune-related genes were identified from medical databases, and common genes were used to construct a protein-protein interaction network (PPI). Potential biomarkers reflecting the clinical features of AD were screened using Pearson correlations and logistic regression analysis. We identified 210 DEGs in the AD group. ImmuCellAI indicated that blood samples from patients with AD had a higher abundance of exhausted T (Tex; 0.196 vs. 0.132) and induced regulatory T (iTreg; 0.180 vs. 0.137) cells than controls. Thirty-two genes overlapped between the BBB and immune-related genes, and 27 genes in the PPI network were associated with eight pathways, including the cytokine-cytokine receptor interaction pathway (hsa04060) and the chemokine signaling pathway (hsa04062). Pearson correlations showed that five genes were associated with the CSF biomarkers, Aβ, total, and phosphorylated tau. Logistics analysis showed that the B cell-associated genes, CXCL12 and TNFRSF13C, were independent risk factors for AD diagnosis. Peripheral CXCL12 and TNFRSF13C genes that correlated with immune cell infiltration in AD might serve as easily accessible biomarkers for the early diagnosis of AD.
神经炎症诱导的神经退行性变和免疫细胞浸润是阿尔茨海默病（AD）的两个特征。本研究旨在鉴定与 AD 中脑脊液（CSF）和浸润免疫细胞相互作用的潜在外周生物标志物。从阿尔茨海默病神经影像学倡议数据库中下载血液和 CSF 数据。我们鉴定了 AD 中的差异表达基因（DEGs），并使用免疫细胞丰度鉴定器（ImmuCellAI）算法评估浸润免疫细胞。从医学数据库中鉴定血脑屏障（BBB）和免疫相关基因，并使用常见基因构建蛋白质-蛋白质相互作用网络（PPI）。使用 Pearson 相关性和逻辑回归分析筛选反映 AD 临床特征的潜在生物标志物。我们在 AD 组中鉴定了 210 个 DEGs。ImmuCellAI 表明，AD 患者的血液样本中耗竭 T（Tex；0.196 比 0.132）和诱导调节性 T（iTreg；0.180 比 0.137）细胞的丰度更高。BBB 和免疫相关基因之间有 32 个基因重叠，PPI 网络中的 27 个基因与包括细胞因子-细胞因子受体相互作用途径（hsa04060）和趋化因子信号通路（hsa04062）在内的 8 个途径相关。Pearson 相关性表明，有 5 个基因与 CSF 生物标志物 Aβ、总蛋白和磷酸化 tau 相关。逻辑分析表明，与 AD 免疫细胞浸润相关的 B 细胞相关基因 CXCL12 和 TNFRSF13C 是 AD 诊断的独立危险因素。与 AD 中免疫细胞浸润相关的外周 CXCL12 和 TNFRSF13C 基因可能作为 AD 早期诊断的容易获取的生物标志物。
