Acupuncture Therapy on Dementia: Explained with an Integrated Analysis on Therapeutic Targets and Associated Mechanisms

Background: Dementia, mainly Alzheimer's disease (AD) and vascular dementia (VaD), remains a global health challenge. Previous studies have demonstrated the benefits of acupuncture therapy (AT) in improving dementia. Nevertheless, the therapeutic targets and integrated biological mechanisms involved remain ambiguous. Objective: To identify therapeutic targets and biological mechanisms of AT in treating dementia by integrated analysis strategy. Methods: By the identification of differentially expressed genes (DEGs) of AD, VaD, and molecular targets of AT active components, the acupuncture therapeutic targets associated with the biological response to AD and VaD were extracted. Therapeutic targets-based functional enrichment analysis was conducted, and multiple networks were constructed. AT-therapeutic crucial targets were captured by weighted gene co-expression network analysis (WGCNA). The interactions between crucial targets with AT active components were verified by molecular docking. Results: Our results demonstrated that 132 and 76 acupuncture therapeutic targets were associated with AD and VaD. AT-therapeutic crucial targets including 58 for AD and 24 for VaD were captured by WGCNA, with 11 in shared, including NMU, GRP, TAC1, ADRA1D, and SST. In addition, 35 and 14 signaling pathways were significantly enriched by functional enrichment analysis, with 6 mutual pathways including neuroactive ligand-receptor interaction, GABAergic synapse, calcium signaling pathway, cAMP signaling pathway, chemokine signaling pathway, and inflammatory mediator regulation of TRP channels. Conclusion: The improvement of AD and VaD by AT was associated with modulation of synaptic function, immunity, inflammation, and apoptosis. Our study clarified the therapeutic targets of AT on dementia, providing valuable clues for complementing and combining pharmacotherapy.