Abstract
Parkinson’s disease (PD) is a common neurodegenerative disease in the elderly with a pathogenesis that remains unclear. We aimed to explore its pathogenesis through plasma integrated metabolomics and proteomics analysis. The clinical data of consecutively recruited PD patients and healthy controls were assessed. Fasting plasma samples were obtained and analyzed using metabolomics and proteomics methods. After that, differentially expressed metabolites and proteins were identified for further bioinformatics analysis. No significant difference was found in the clinical data between these two groups. Eighty-three metabolites were differentially expressed in PD patients identified by metabolomics analysis. These metabolites were predominately lipid and lipid-like molecules (63%), among which 25% were sphingolipids. The sphingolipid metabolism pathway was enriched and tended to be activated in the following KEGG pathway analysis. According to the proteomics analysis, forty proteins were identified to be differentially expressed, seven of which were apolipoproteins. Furthermore, five of the six top ranking Gene Ontology terms from cellular components and eleven of the other fourteen Gene Ontology terms from biological processes were directly associated with lipid metabolism. In KEGG pathway analysis, the five enriched pathways were also significantly related with lipid metabolism (p < 0.05). Overall, Parkinson’s disease is associated with plasma lipid metabolic disturbance, including an activated sphingolipid metabolism and decreased apolipoproteins.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disease and is expected to affect 14.2 million people worldwide by 2040 (Dorsey and Bloem, 2018)
Thirty-six PD patients and healthy controls were separately included in the metabolomics analysis
No significant differences were observed between these two groups, including the levels of hemoglobin A1C (HbA1C) and blood lipid, or the incidences of diabetes mellitus and hypercholesterolemia
Summary
Parkinson’s disease (PD) is a common neurodegenerative disease and is expected to affect 14.2 million people worldwide by 2040 (Dorsey and Bloem, 2018). Lipid Metabolic Disturbance in Parkinson’s Disease with many non-motor symptoms, some of which even precede the motor symptoms by more than 10 years, including constipation, hyposmia, anxiety, depression, and rapid eye movement sleep behavior disorder (Emamzadeh and Surguchov, 2018). These non-motor symptoms are probably due to the disturbance of various neurotransmitters and multiple nerve systems in addition to the dopaminergic neurons in the SNpc (Lv and Ae, 2015). Results of genome-wide association studies have identified 90 independent mutations in more than 20 genes that increase risk factors for Parkinson’s disease (Blauwendraat et al, 2019). The interactions between environmental and genetic risk factors are still under investigation
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