Searching for Potential Lipid Biomarkers of Parkinson’s Disease in Parkin-Mutant Human Skin Fibroblasts by HILIC-ESI-MS/MS: Preliminary Findings

Abstract

Early diagnosis of neural changes causing cerebral impairment is critical for proposing preventive therapies for Parkinson’s disease (PD). Biomarkers currently available cannot be informative of PD onset since they are characterized by analysing post-mortem tissues from patients with severe degeneration of the substantia nigra. Skin fibroblasts (SF) are now recognized as a useful model of primary human cells, capable of reflecting the chronological and biological aging of the subjects. Here a lipidomic study of easily accessible primary SF is presented, based on hydrophilic interaction liquid chromatography coupled to electrospray ionization and mass spectrometry (HILIC/ESI-MS). Phospholipids (PL) from dermal fibroblasts of five PD patients with different parkin mutations and healthy control SF were characterized by single and tandem MS measurements using a hybrid quadrupole-Orbitrap and a linear ion trap mass analysers. The proposed approach enabled the identification of more than 360 PL. Univariate statistical analyses highlight abnormality of PL metabolism in the PD group, suggesting down- or up-regulation of certain species according to the extent of disease progression. These findings, although preliminary, suggest that the phospholipidome of human SF represents a source of potential biomarkers for the early diagnosis of PD. The dysregulation of ethanolamine plasmalogens in the circulatory system, especially those containing polyunsaturated fatty acids (PUFA), might be likely associated with neurodegeneration.