Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s disease
Abstract Emerging evidence suggests that dysregulation of lipid metabolism and chronic inflammation in the central nervous system (CNS) contribute to the risk of Parkinson’s disease (PD). However, the causal relationship between plasma lipid metabolism and PD, particularly through immune modulation,...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-12054-y |
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| author | Daoqing Su Yajun Jing Jinye Su Honglin Zhu Yiming Chen Qiu He Dengliang Wang Dezhi Kang Yuanxiang Lin |
| author_facet | Daoqing Su Yajun Jing Jinye Su Honglin Zhu Yiming Chen Qiu He Dengliang Wang Dezhi Kang Yuanxiang Lin |
| author_sort | Daoqing Su |
| collection | DOAJ |
| description | Abstract Emerging evidence suggests that dysregulation of lipid metabolism and chronic inflammation in the central nervous system (CNS) contribute to the risk of Parkinson’s disease (PD). However, the causal relationship between plasma lipid metabolism and PD, particularly through immune modulation, remains unclear. In this study, we used Mendelian randomization (MR) to investigate the causal association between plasma lipidome and PD risk, utilizing GWAS summary statistics for PD, circulating immune cells, inflammatory proteins, and plasma lipidome. We found that higher plasma phosphatidylcholine (17:0_18:1) levels were causally associated with an increased risk of PD, with a 1 standard deviation genetically instrumented higher level corresponding to a 30% increased risk (95% CI 1.05–1.61, p = 0.014). Multivariate Mendelian randomization (MVMR) analysis confirmed this association after adjusting for triacylglycerol levels. Mediation analysis revealed that the causal link between plasma phosphatidylcholine and PD was mediated by circulating immune cells (specifically CD45 on CD14+ monocytes and CD45 on HLA-DR+ T cells) rather than by circulating inflammatory proteins. These findings highlight a novel pathway linking lipid metabolism, immune modulation, and PD risk. |
| format | Article |
| id | doaj-art-7f92ee90a7134e7c86353cf1fd601bcc |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7f92ee90a7134e7c86353cf1fd601bcc2025-08-20T03:46:04ZengNature PortfolioScientific Reports2045-23222025-08-0115111210.1038/s41598-025-12054-yHigher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s diseaseDaoqing Su0Yajun Jing1Jinye Su2Honglin Zhu3Yiming Chen4Qiu He5Dengliang Wang6Dezhi Kang7Yuanxiang Lin8Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityFaculty of Life Sciences and Medicine, King’s College LondonDepartment of Medical Laboratory, College of Medical Technology and Engineering, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityDepartment of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical UniversityAbstract Emerging evidence suggests that dysregulation of lipid metabolism and chronic inflammation in the central nervous system (CNS) contribute to the risk of Parkinson’s disease (PD). However, the causal relationship between plasma lipid metabolism and PD, particularly through immune modulation, remains unclear. In this study, we used Mendelian randomization (MR) to investigate the causal association between plasma lipidome and PD risk, utilizing GWAS summary statistics for PD, circulating immune cells, inflammatory proteins, and plasma lipidome. We found that higher plasma phosphatidylcholine (17:0_18:1) levels were causally associated with an increased risk of PD, with a 1 standard deviation genetically instrumented higher level corresponding to a 30% increased risk (95% CI 1.05–1.61, p = 0.014). Multivariate Mendelian randomization (MVMR) analysis confirmed this association after adjusting for triacylglycerol levels. Mediation analysis revealed that the causal link between plasma phosphatidylcholine and PD was mediated by circulating immune cells (specifically CD45 on CD14+ monocytes and CD45 on HLA-DR+ T cells) rather than by circulating inflammatory proteins. These findings highlight a novel pathway linking lipid metabolism, immune modulation, and PD risk.https://doi.org/10.1038/s41598-025-12054-yLipid metabolismParkinson’s diseaseCirculating inflammatory proteinsCirculating immune cellsMendelian randomization analysis |
| spellingShingle | Daoqing Su Yajun Jing Jinye Su Honglin Zhu Yiming Chen Qiu He Dengliang Wang Dezhi Kang Yuanxiang Lin Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s disease Scientific Reports Lipid metabolism Parkinson’s disease Circulating inflammatory proteins Circulating immune cells Mendelian randomization analysis |
| title | Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s disease |
| title_full | Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s disease |
| title_fullStr | Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s disease |
| title_full_unstemmed | Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s disease |
| title_short | Higher levels of plasma phosphatidylcholine (17:0_18:1) raise the risk of developing Parkinson’s disease |
| title_sort | higher levels of plasma phosphatidylcholine 17 0 18 1 raise the risk of developing parkinson s disease |
| topic | Lipid metabolism Parkinson’s disease Circulating inflammatory proteins Circulating immune cells Mendelian randomization analysis |
| url | https://doi.org/10.1038/s41598-025-12054-y |
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