Dissecting causal and putative mechanistic pathways from lifestyle factors to neurological diseases via the glymphatic system: a Mendelian randomization study.

OBJECTIVE

This study aimed to investigate the causal associations and potential mechanistic pathways involving pulse rate, neuronal cell adhesion molecule (NrCAM), migraine, and other neurological disorders within the context of the glymphatic system.

METHODS AND

RESULTS

Using bidirectional two-sample Mendelian randomization analysis, we constructed simple, parallel, and serial causal pathway diagrams based on significant genetic evidence, in combination with a disease network approach, to elucidate key relationships and plausible biological routes. Key findings indicate that pulse rate influences NrCAM expression, and NrCAM mediates the development of migraine. Neurological disorders such as stroke and Parkinson's disease were found to impact related molecular pathways. The study identifies NrCAM as a pivotal molecule in the glymphatic system, influenced by lifestyle factors and contributing to migraine pathogenesis. Moreover, pulse rate acts as an initiating factor driving molecular changes, with neurological disorders serving as mediators in the causal network.

CONCLUSION

The complex interplay between lifestyle, physiological factors, molecular mediators, and neurological disorders reveals an intricate network of causality in neurological disease. These findings underscore the importance of optimizing glymphatic function and highlight NrCAM as a potential therapeutic target. Understanding these interactions provides insights for developing targeted interventions and personalized treatment strategies for neurological disease prevention and management.