International journal of biological macromoleculesSep 26, 2025

Combining multiple biological data types reveals important small RNAs, immune inflammation, and communication pathways in Alzheimer's disease linked to targeted treatment

Regenerative Health Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 7, 2026

Abstract

Four differentially expressed miRNAs were identified in relation to Alzheimer's disease.

The identified miRNAs (miR-339-3p, miR-28-3p, miR-423-3p, miR-144-5p) are associated with synaptic function and immune-inflammatory responses.
A total of 725 mRNAs linked to Alzheimer's disease were found, implicating immune and apoptosis pathways.
Altered proportions of immune cells were observed in the blood of Alzheimer's disease patients, suggesting systemic immunodysregulation.
Three integrated omics datasets revealed 388 key genes involved in signaling pathways such as JAK-STAT, PI3K-Akt, and MAPK.
Combining candidate miRNAs was shown to significantly reduce markers associated with Alzheimer's disease while promoting certain neuron progenitor cell markers.

Simplified

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.

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Declaration of competing interest The authors declare no competing interests.

PubMed

Combining multiple biological data types reveals important small RNAs, immune inflammation, and communication pathways in Alzheimer's disease linked to targeted treatment

Abstract

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