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Targeted Lipidomics Reveals Lipid Remodelling in Parkinson’s Disease
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Targeted Lipidomics Reveals Lipid Remodelling in Parkinson’s Disease

Jack Price
Murdoch University
Masters by Research, Murdoch University
2025
DOI:
https://doi.org/10.60867/00000078
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Abstract

Parkinson's Disease Lipids--Analysis Lipids--Metabolism
Parkinson’s Disease (PD) is a progressive, neurodegenerative condition that is increasing in prevalence globally. PD is marked by a loss of dopaminergic neurons in the brain, but system-wide metabolic disturbances are now understood to contribute to disease aetiogenesis. Importantly, whilst the clinical presentation of PD is highly heterogenous, a metabolic basis for stratification into different subtypes is lacking. As such, readily accessible biomarkers of PD that can give insight into disease status are highly sought after to address shortcomings in existing approaches that result in poor diagnostic accuracy, minimal treatment options, and a limited understanding of the disease process. This study explored the serum lipidome of sporadic PD cases with age and sex matched controls (n = 116, 58 PD; 58 control) in an Estonian cohort. Targeted liquid chromatography-tandem mass spectrometry was employed to detect 780 lipid species spanning 18 classes. Multivariate and univariate analyses indicate a significant perturbation of lipid metabolism in the PD group. The main serum lipids separating the PD group from the control group belonged to the glycerolipids (triacylglycerides and diacylglycerides) and glycerophospholipids (phosphatidylglycerol, phosphatidylserines, and phosphatidylethanolamines) classes, and were decreased in PD patients, whilst lyso- phospolipids (LPI, LPE, and LPC) were increased in the PD group. Investigation of individual lipid species reveals a marked remodelling of glycerolipids and glycerophospholipids, with significant reductions to esterified forms of arachidonic, adrenic, docosapentanoic, and docosahexaenoic acids. These findings suggest activation of inflammatory pathways and provide further evidence of perturbed lipid metabolism in PD. Future work in this area can elucidate the mechanistic causes behind these changes and investigate new targets for treatment.

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