2. Academic Validation
  3. Multi-omics integration reveals key miRNAs, immune inflammation, and signaling pathways in Alzheimer's disease: Implications for targeted therapy

Multi-omics integration reveals key miRNAs, immune inflammation, and signaling pathways in Alzheimer's disease: Implications for targeted therapy

  • Int J Biol Macromol. 2025 Sep 24;329(Pt 2):147874. doi: 10.1016/j.ijbiomac.2025.147874.
Guodong Wang 1,  Jiawen Duan 1,  Longfei Sun 1,  Siyao Pan 1,  Quanhui Liu 2,  Kaijing Fu 3,  Dandan Zhang 1,  Xiang Yuan 1,  Binglin Fan 4,  Beiquan Hu 5,  Ben Huang 6
Affiliations

Affiliations

  • 1 Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning, 530021, China.
  • 2 School of Animal Science and Technology, Guangxi University, Nanning, 530005, Guangxi, China.
  • 3 Department of Functional Neurosurgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
  • 4 Department of Geriatric Neurology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China. Electronic address: fbl_1180@163.com.
  • 5 Department of Functional Neurosurgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China. Electronic address: ynhhhb@163.com.
  • 6 Guangxi Zhuang Autonomous Region Engineering Research Center for 3D Printing in Smart Biomanufacturing and Application, Guangxi Academy of Medical Sciences, Nanning, 530021, China. Electronic address: benhuang@gxu.edu.cn.
PMID: 41005404 DOI: 10.1016/j.ijbiomac.2025.147874
Abstract

Alzheimer's disease (AD), a common neurodegenerative disorder, has unclear molecular mechanisms and therapeutic targets. In this study, multi-omics analysis and experimental validation were performed. By integrating three miRNA-seq, four differentially expressed miRNAs (miR-339-3p, miR-28-3p, miR-423-3p, miR-144-5p) were identified, closely related to synaptic function and immune-inflammatory responses. By integrating blood RNA-seq data, we found 725 mRNAs linked to AD, immune, and Apoptosis pathways. Peripheral blood single-cell transcriptomics showed altered immune cell proportions in AD patients, indicating systemic immunodysregulation. Integrating the three omics datasets identified 388 key genes involved in JAK-STAT, PI3K-Akt, and MAPK pathways. Experimental validation showed that combining candidate miRNAs significantly reduced AD marker expression and promoted neuronal progenitor cell marker expression, but had limited effect on mature neuronal markers (MAP2, NeuN). However, providing a suitable neuronal environment could induce neuronal differentiation, showing neuronal induction potential. These findings reveal the dual role of synaptic dysfunction and neuroinflammation in AD progression, offering new insights into AD's molecular network and proposing a treatment framework combining immunomodulation and neuroregeneration.

Keywords

AD cellular models; AD therapeutic targets; Alzheimer's disease; Multi-omics integrative analysis; miRNA.

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