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Peer-reviewedCC BY-NC-ND 4.0Neurotherapeutics

Multi-omics analysis of potential therapeutic targets for Alzheimer’s disease and associated differences in immune cell infiltration

  • Wanqian Xu1
  • Min Liu2
  • Xiajing Yu3
  • Yun Hao4
  • Zheng Fu5
  • Linfeng Jin3
  • Hui Liang5
  • Kaili Liao6
  • Xiaozhong Wang7
  • Jiasheng Xu8
8 affiliations
  1. 1Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China; Queen Mary College, Jiangxi Medical College, Nanchang University, Xuefu Road, Nanchang, Jiangxi, 330006, China
  2. 2Department of Biophysics and Neurology, Center for Membrane Receptors and Brain Medicine, The Fourth Affiliated Hospital of School of Medicine, And International School of Medicine, International Institutes of Medicine, Zhejiang University, Yiwu, Zhejiang, 322000, China; Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou, 310058, China
  3. 3Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China; The Second Clinical Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
  4. 4Queen Mary College, Jiangxi Medical College, Nanchang University, Xuefu Road, Nanchang, Jiangxi, 330006, China
  5. 5The First Clinical Medical College, Nanchang University, Xuefu Road, Nanchang, Jiangxi, 330006, China
  6. 6Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China
  7. 7Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China; Corresponding author.
  8. 8Department of Gastroenterology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, China; Corresponding author.
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Abstract

Alzheimer’s disease (AD) represents a progressive neurodegenerative disorder that predominantly impairs the central nervous system. This study integrated single-cell RNA sequencing (scRNA-seq) and Mendelian randomization (MR) analysis to explore AD therapeutic targets and characterize alterations in immune cell infiltration and function. We analyzed the subtypes, developmental trajectories and intercellular communication of peripheral blood T cells from AD scRNA-seq data. Cell clustering identified CD8 + T cells as the key immune subpopulation in AD, with two vital intercellular communication pathways (MIF-(CD74 + CD44) and MIF-(CD74 + CXCR4)) identified by trajectory analysis. The expression quantitative trait loci (eQTL) data retrieved from the IEU OpenGWAS database were utilized to perform MR and colocalization analysis to evaluate the association between target genes and AD. Six multiple-SNP and one single-SNP potential target genes were screened via differential expression and MR analysis. Among these, dual-specificity phosphatase 2 (DUSP2) showed a suggestive but weak association with AD, with a mild positive correlation observed in sensitivity analyses. No statistically significant shared genetic signals were detected via colocalization analysis. Additionally, significant differences in intercellular communication were observed between DUSP2+IM and DUSP2-IM cells, with distinct activity across various communication pathways. Gene expression levels in the AD group were significantly higher than in healthy individuals (P = 0.01). In conclusion, this study identified CD8 + T cells as crucial factors in AD pathogenesis, while DUSP2 emerged as a suggestive candidate gene requiring further validation, providing novel mechanistic insights and potential therapeutic targets for AD treatment.

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Cite

BibTeXRIS
BibTeX
@article{xu2026multiomics,
  title = {{Multi-omics analysis of potential therapeutic targets for Alzheimer’s disease and associated differences in immune cell infiltration}},
  author = {Wanqian Xu and Min Liu and Xiajing Yu and Yun Hao and Zheng Fu and Linfeng Jin and Hui Liang and Kaili Liao and Xiaozhong Wang and Jiasheng Xu},
  journal = {Neurotherapeutics},
  year = {2026},
  month = oct,
  doi = {10.1016/j.neurot.2026.e01092},
  url = {https://doi.org/10.1016/j.neurot.2026.e01092},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Multi-omics analysis of potential therapeutic targets for Alzheimer’s disease and associated differences in immune cell infiltration
AU  - Wanqian Xu
AU  - Min Liu
AU  - Xiajing Yu
AU  - Yun Hao
AU  - Zheng Fu
AU  - Linfeng Jin
AU  - Hui Liang
AU  - Kaili Liao
AU  - Xiaozhong Wang
AU  - Jiasheng Xu
PY  - 2026
DA  - 2026/10/22
JO  - Neurotherapeutics
DO  - 10.1016/j.neurot.2026.e01092
UR  - https://doi.org/10.1016/j.neurot.2026.e01092
AB  - Alzheimer’s disease (AD) represents a progressive neurodegenerative disorder that predominantly impairs the central nervous system. This study integrated single-cell RNA sequencing (scRNA-seq) and Mendelian randomization (MR) analysis to explore AD therapeutic targets and characterize alterations in immune cell infiltration and function. We analyzed the subtypes, developmental trajectories and intercellular communication of peripheral blood T cells from AD scRNA-seq data. Cell clustering identified CD8 + T cells as the key immune subpopulation in AD, with two vital intercellular communication pathways (MIF-(CD74 + CD44) and MIF-(CD74 + CXCR4)) identified by trajectory analysis. The expression quantitative trait loci (eQTL) data retrieved from the IEU OpenGWAS database were utilized to perform MR and colocalization analysis to evaluate the association between target genes and AD. Six multiple-SNP and one single-SNP potential target genes were screened via differential expression and MR analysis. Among these, dual-specificity phosphatase 2 (DUSP2) showed a suggestive but weak association with AD, with a mild positive correlation observed in sensitivity analyses. No statistically significant shared genetic signals were detected via colocalization analysis. Additionally, significant differences in intercellular communication were observed between DUSP2+IM and DUSP2-IM cells, with distinct activity across various communication pathways. Gene expression levels in the AD group were significantly higher than in healthy individuals (P = 0.01). In conclusion, this study identified CD8 + T cells as crucial factors in AD pathogenesis, while DUSP2 emerged as a suggestive candidate gene requiring further validation, providing novel mechanistic insights and potential therapeutic targets for AD treatment.
SN  - 1878-7479
SN  - 1933-7213
ER  -