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Lipid pathway dysfunction is prevalent in patients with Parkinson's disease
Jasmin Galper1, Nicholas J Dean2, Russell Pickford3
1Brain and Mind Centre and Faculty of Medicine and Health, School of Medical Sciences, University of Sydney, Camperdown, NSW 2050, Australia.
Brain : a Journal of Neurology
|May 13, 2022
Summary
Parkinson's disease involves lipid dysregulation, particularly in LRRK2 mutation carriers. Altered lipid pathways suggest new therapeutic targets and potential serum biomarkers for Parkinson's disease.
Area of Science:
- Neuroscience
- Metabolomics
- Genetics
Background:
- Genetic Parkinson's disease (PD) risk factors often involve lipid functions.
- Lipid-modulating drugs may offer protection against PD.
- Alpha-synuclein, central to PD pathology, interacts with lipid membranes.
Purpose of the Study:
- To investigate lipid dysregulation in Parkinson's disease, including LRRK2 mutation carriers.
- To identify specific lipid species and pathways affected in PD.
- To explore the potential of serum lipid profiles as biomarkers for PD.
Main Methods:
- Untargeted high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) on serum and cerebrospinal fluid (CSF).
- Analysis of a multi-ethnic cohort including controls, LRRK2 G2019S carriers (asymptomatic and with PD), and non-LRRK2 PD patients.
- Pathway analysis to identify dysregulated metabolic pathways.
Main Results:
- Distinct lipid profiles in PD patients and LRRK2 carriers compared to controls, with alterations in ceramides, triacylglycerols, sphingomyelins, and others.
- Significant changes in sphingolipids and glycerolipids observed in both serum and CSF.
- Pathway analysis revealed dysregulation in sphingolipid metabolism, insulin signaling, and mitochondrial function in PD, corroborated in a second cohort.
Conclusions:
- Dysregulated lipid pathways are implicated in Parkinson's disease, including in LRRK2 mutation carriers.
- These findings suggest potential therapeutic targets for manipulating lipid metabolism in PD.
- Serum lipid profiles may serve as novel biomarkers for both genetic and idiopathic Parkinson's disease.
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