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Peripheral Blood Biomarkers CXCL12 and TNFRSF13C Associate with Cerebrospinal Fluid Biomarkers and Infiltrating Immune Cells in Alzheimer Disease

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Abstract

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.

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Data Availability

The original microarray datasets of Alzheimer disease (including GSE4226, GSE4229, and GSE18309) are available from the National Center of Biotechnology Information Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/). Peripheral blood, CSF, and plasma data of patients with Alzheimer disease and controls were downloaded from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu/).

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Funding

This work was supported by Natural Science Foundation of Shanghai (No.18ZR1417200, obtained by Wei Kong) and National Natural Science Foundation of China (No.61803257; obtained by Shuaiqun Wang).

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  1. Qianqian Wu and Wei Kong are co-first authors of this paper.

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  1. College of Information Engineering, Shanghai Maritime University, Shanghai, 201306, People’s Republic of China

    Qianqian Wu, Wei Kong & Shuaiqun Wang

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  1. Qianqian Wu
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  2. Wei Kong
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Contributions

Conception and design of the research: Qianqian Wu and Wei Kong. Acquisition, analysis, and interpretation of data: Qianqian Wu, Shuaiqun Wang, and Wei Kong. Statistical analysis: Qianqian Wu. Drafting the manuscript: Qianqian Wu. Manuscript revision for important intellectual content: Wei Kong. All authors have read and approved the manuscript.

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Correspondence to Wei Kong.

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Wu, Q., Kong, W. & Wang, S. Peripheral Blood Biomarkers CXCL12 and TNFRSF13C Associate with Cerebrospinal Fluid Biomarkers and Infiltrating Immune Cells in Alzheimer Disease. J Mol Neurosci 71, 1485–1494 (2021). https://doi.org/10.1007/s12031-021-01809-7

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