Conclusions
Our study demonstrated that the disturbed composition and function of CSF-derived exosome lipidome during the pathological stage of PD may affect different types of sleep disorder in PD.
Methods
We used a non-targeted lipidomics to explore the lipid composition of cerebrospinal fluid (CSF) exosomes derived from patients with PD carrying phospholipase A2 Group VI (PLA2G6) and sphingomyelin phosphodiesterase 1 (SMPD1) mutations.
Results
PLA2G6 mutations (c.1966C > G, Leu656Val; c.2077C > G, Leu693Val; c.1791delC, His597fx69) significantly increase the exosomal content of glycerophospholipids and lysophospholipids, specifically phosphatidylcholine (PC) and lysophosphatidylcholine (LPC). Exosome surface presence of melatomin receptor 1A (MTNR1A) was detectable only in patients with PLA2G6 mutations. We have further shown that, in patients with PD carrying PLA2G6 mutations, sleep latency was significantly longer compared to those carrying WT PLA2G6, and we speculate that functional PLA2G6 mutations lead to structural changes and lipid deregulation of exosomes, which in turn alters exosomal cargo and affects PD-related sleep disorders. In SMPD1, G508R variant-carrying patients with PD abundance of sphingomyelins was significantly higher and had significantly shorter rapid eye movement sleep. Conclusions: Our study demonstrated that the disturbed composition and function of CSF-derived exosome lipidome during the pathological stage of PD may affect different types of sleep disorder in PD.