Serum Phospholipid Profile Changes in Gaucher Disease and Parkinson’s Disease

Abstract

Alterations in the levels of serum sphingolipids and phospholipids have been reported in Gaucher disease and in Parkinson’s disease, suggesting a potential role of these lipids as biomarkers. This project’s objective is to detect novel associations and novel candidate biomarkers in the largest Spanish Gaucher and Parkinson diseases of the Iberian Peninsula. For that, 278 participants were included: 100 sporadic Parkinson’s patients, 70 Gaucher patients, 15 GBA1-mutation-carrier Parkinson’s patients and 93 controls. A serum lipidomics array including 10 phospholipid groups, 368 species, was performed using high-performance liquid chromatography–mass spectrometry. Lipid levels were compared between groups via multiple-regression analyses controlling for clinical and demographic parameters. Additionally, lipid levels were compared within the Gaucher and Parkinson’s groups controlling for medication and/or disease severity. Results were controlled for robustness by filtering of non-detectable lipid values. There was an increase in the levels of phosphatidylcholine, with a simultaneous decrease in lyso-phosphatidylcholine, in the Gaucher, Parkinson’s and GBA1-mutation-carrier Parkinson’s patients vs. controls. Phosphatidylethanolamine, lyso- and plasmalogen-phosphatidylethanolamine were also increased in Gaucher and Parkinson’s. Gaucher patients also showed an increase in lyso-phosphatidylserine and phosphatidylglycerol. While in the Gaucher and Parkinson’s groups, velaglucerase alpha and dopamine agonists, respectively, showed positive associations with the lipid changes, miglustat treatment in Gaucher patients normalized the altered phosphatidylcholine/lyso-phosphatidylcholine ratio. In conclusion, Gaucher and Parkinson’s patients showed changes in various serum phospholipid levels when compared with healthy controls, further supporting the role of such lipids in disease development and, possibly, as putative biomarkers. This hypothesis was reinforced by the normalizing effect of miglustat, and by controlling for data robustness, even though the limited number of participants, especially in the sub-distribution by treatment groups in GD requires validation in a larger number of patients.

The Role of Alpha-Synuclein in Synucleinopathy: Impact on Lipid Regulation at Mitochondria–ER Membranes

“…Furthermore, a meta-analysis of differentially expressed genes in patients with PD identified the downregulation of PSS1 in the SNpc (57), suggesting that although dysregulated PS is involved in pathogenesis, the cell may compensate for phospholipid defects through multiple mechanisms. As reported by us and others, data suggest that these PS alterations are deeply associated with αSyn pathology and neurological deficits (58–60), in agreement with previous observations (61–63). On the other hand, these data do not clarify whether these phospholipid alterations occur in all cell types in most affected brain areas or just in populations with higher levels of αSyn aggregates.…”

Biomarker discovery in galactosemia: Metabolomics with UPLC/HRMS in dried blood spots

“…In the heatmap, the top 25 metabolites with the most significant differences in abundance between the groups were visualized and identified as potential biomarkers for GAL. Among these metabolites, phosphatidylethanolamine, which is a category of phospholipids present in biological membranes, was found to be the most significantly upregulated metabolite in the GAL group, confirming the increase of phosphatidylethanolamine in complications of GAL such as neurological impairments and cataracts (Jernigan Jr et al, 2005;López de Frutos et al, 2022).…”