Plasma oxylipin profiles reflect Parkinson's disease stage

Derivatives of polyunsaturated fatty acids (PUFAs), also known as oxylipins, are key participants in regulating inflammation. Neuroinflammation is involved in many neurodegenerative diseases, including Parkinson's disease. The development of ultra-high-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) facilitated the study of oxylipins on a system level, i.e., the analysis of oxylipin profiles. We analyzed oxylipin profiles in the blood plasma of 36 healthy volunteers (HC) and 73 patients with Parkinson's disease (PD), divided into early (L\M, 29 patients) or advanced (H, 44 patients) stages based on the Hoehn and Yahr scale. Among the 40 oxylipins detected, we observed a decrease in the concentration of arachidonic acid (AA) and AA derivatives, including anandamide (AEA) and Leukotriene E4 (LTE4), and an increase in the concentration of hydroxyeicosatetraenoic acids 19-HETE and 12-HETE (PD vs HC). Correlation analysis of gender, age of PD onset, and disease stages revealed 20 compounds the concentration of which changed depending on disease stage. Comparison of the acquired oxylipin profiles to openly available PD patient brain transcriptome datasets showed that plasma oxylipins do not appear to directly reflect changes in brain metabolism at different disease stages. However, both the L\M and H stages are characterized by their own oxylipin profiles - in patients with the H stage oxylipin synthesis is increased, while in patients with L\M stages oxylipin synthesis decreases compared to HC. This suggests that different therapeutic approaches may be more effective for patients at early versus late stages of PD.