Imagine a jigsaw puzzle where two seemingly different pieces fit together perfectly to reveal a hidden connection. In a similar way, scientists have unraveled the underlying molecular signatures shared by vascular dementia (VaD) and carotid plaques, shedding light on potential drug targets for both conditions. VaD and carotid plaques are two separate health issues affecting the elderly population, but researchers discovered that they share 41 common genes that are differentially expressed. These genes are primarily involved in inflammatory and immune-related processes, suggesting that inflammation plays a crucial role in both conditions. The study also identified specific immune cells that infiltrate carotid plaques and the brains of VaD patients, further supporting the connection between the two. Interestingly, through advanced analysis techniques, researchers pinpointed 12 key genes closely related to these immune cells. Finally, the researchers explored drug-gene interactions and identified four potential drugs that could target the shared mechanisms of VaD and carotid plaques. This exciting study opens up new possibilities for improving treatments for both conditions and brings us closer to solving the puzzle of their connection!

BackgroundVascular dementia (VaD) and carotid atherosclerotic plaques are common in the elderly population, conferring a heavy burden on families and society. Accumulating evidence indicates carotid atherosclerotic plaques to be a risk factor for VaD. However, the underlying mechanisms for this association are mainly unknown.Materials and methodsWe analyzed temporal cortex gene expression data of the GSE122063 dataset and gene expression data of the GSE163154 dataset to identify commonly differentially expressed genes (DEGs). Then we performed functional enrichment analysis, immune cell infiltration and evaluation, correlation analysis between differentially expressed immune-related genes (DEIRGs) and immune cells, receiver operating characteristic (ROC) analysis, and drug-gene analysis.ResultsWe identified 41 overlapped DEGs between the VaD and carotid atherosclerosis plaque datasets. Functional enrichment analyses revealed that these overlapped DEGs were mainly enriched in inflammatory and immune-related processes. Immunocyte infiltration and evaluation results showed that M0 macrophages, M2 macrophages, and T cells gamma delta had a dominant abundance in carotid atherosclerosis plaque samples, and M0 macrophages showed a significantly different infiltration percentage between the early and advanced stage plaques group. Resting CD4 memory T cells, M2 macrophages, and naive B cells were the top three highest infiltrating fractions in VaD. Furthermore, B cells and NK cells showed a different infiltration percentage between VaD and matched controls. We identified 12 DEIRGs, and the result of correlation analysis revealed that these DEIRGs were closely related to differentially expressed immune cells. We identified five key DEIRGs based on ROC analysis. The drug-gene interaction analysis showed that four drugs (avacopan, CCX354, BMS-817399, and ASK-8007) could be potential drugs for VaD and carotid atherosclerotic plaques treatment.ConclusionCollectively, these findings indicated that inflammatory and immune-related processes be a crucial common pathophysiological mechanism shared by VaD and carotid plaques. This study might provide new insights into common molecular mechanisms between VaD and carotid plaques and potential targets for the treatment.

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