Serum lipidomics reveals class-specific lipid remodelling and altered acyl chain composition in Parkinson's disease

Lipid metabolism is increasingly implicated in Parkinson's Disease (PD) pathology, yet the specific lipid classes and acyl chain compositions involved, and their relationship with PD clinical symptoms, remain poorly characterised.

We aimed to identify serum lipid signatures that differentiate people with PD (PwPD) from healthy controls and to evaluate associations with levodopa-induced dyskinesia (LID).

Serum collected from 58 PwPD and 58 age- and sex-matched non-PD controls was analysed using targeted liquid chromatography - mass spectrometry (LC-MS). Group differences were assessed using univariate and multivariate approaches. Logistic regression was used to identify lipids associated with LID among PwPD.

Significantly lower levels of glycerolipids and glycerophospholipids were observed in PwPD compared to controls, alongside higher levels of lysophosphatidylethanolamines (LPE) and lysophosphatidylcholines (LPC). Analysis of individual lipid species revealed a lipid remodelling of the acyl chain composition of glycerolipids and glycerophospholipids, with decreased esterified arachidonic, adrenic, docosapentaenoic, and docosahexaenoic acids. Non-esterified arachidonic acid (p = 5.80e-6) and eicosapentaenoic acid (p = 3.65e-10) were elevated in PwPD. In secondary analyses, no lipids discriminated between PwPD with and without LID; however, these models were constrained by modest subgroup sizes and clinical heterogeneity between groups, limiting conclusions regarding lipid-based discrimination of LID status.

These findings demonstrate disease-associated remodelling of acyl chain composition across multiple lipid classes in PD, particularly selective depletion of esterified polyunsaturated fatty acids from glycerolipids and glycerophospholipids. Replication in independent cohorts is warranted to establish whether these pathways represent viable therapeutic targets.