Causal relationships between plasma lipidomics, trace elements, cerebrospinal fluid metabolites, and Parkinson's disease using Mendelian randomization

OBJECTIVE: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra, leading to motor dysfunction and non-motor symptoms such as dementia, depression, and anxiety. Despite numerous studies on the prevention and treatment of PD, the causal relationships between plasma lipids, trace elements, cerebrospinal fluid (CSF) metabolites and PD remain unclear. METHODS: This study employed Mendelian Randomization (MR) analysis using large European population samples to examine these relationships. RESULTS: We identified 17 lipid phenotypes, 2 trace elements (Selenium and Iridium), and 8 CSF metabolites that have a significant causal association with PD. Lipid phenotypes such as Triacylglycerol and Phosphatidylcholine were found to be protective against PD, while Sphingomyelin and other lipid types were identified as pathogenic. Selenium has been shown to have a protective effect, while Iridium is negatively associated with the progression of PD, suggesting a different role than other heavy metals.Our mediation analysis also revealed that these lipids could influence PD through their effects on CSF metabolites. For instance, Phosphatidylcholine and Uridine were found to protect neurons and improve PD prognosis, whereas no consistent mediation effect was observed for trace elements. CONCLUSION: Overall, our results provide new insights into the complex relationships between plasma lipids, trace elements and CSF metabolites and PD. These results offer potential pathways for future research and provide valuable information for the prevention and treatment of PD.