Periodontitis Exacerbates Cognitive Impairment via Endothelial Inflammation: Insights from Single-Nucleus Transcriptomics.

Objective: To explore the underlying mechanisms of the association between periodontitis and cognitive impairment.

Methods: Single-nucleus transcriptomics of mice were used to investigate the impact of periodontitis on brain and hippocampal cells to gain insights into disease progression. After data processing, functional enrichment, pathway analysis and cell-cell communication analysis were used to identify the distinct pathways and genes upregulated in Alzheimer's disease (AD) linked to periodontitis. After cell culture, real-time quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to confirm the results.

Results: The present authors identified endothelial inflammation as a key factor in periodontitis-related AD. The findings revealed that the upregulation of Mgll expression in endothelial cells was linked to increased antigen presentation and exacerbated neuroinflammation, potentially worsening AD. Moreover, the present authors elucidated MGLL-2AG-CB2 signalling, through which MGLL activation suppresses CB2 expression and leads to heightened inflammation, while MGLL inhibition restores CB2 levels and mitigates inflammation.

Conclusion: The present study revealed the role of MGLL in linking periodontitis to hippocampal endothelial inflammation and antigen presentation in cognitive impairment. This research will enhance the understanding of how periodontitis impacts cognition and explore potential therapeutic strategies to alleviate periodontitis-associated cognitive impairment.