engleski

Glycosylation profiling in plasma of patients with Parkinson’s disease reveals putative biomarkers

Most proteins are known to be glycosylated and glycans play important structural, functional and regulatory roles in various physiological processes. Glycosylation is not the simple addition of glycan decorations, but a carefully orchestrated process resulting in the creation of specific branched glycans that significantly affect protein structure and function. Glycan biomarkers have been identified in a range of diseases, but the knowledge about their possible role in Parkinson’s disease (PD) is still limited. In order to ascertain the putative role glycosylation plays in development and progression of PD, we performed the first comprehensive analysis of human plasma glycome in PD patients. Glycosylation analysis was performed in plasma samples of 199 PD patients and 47 control individuals using high performance liquid chromatography (HPLC). Additionally, we compared the glycosylation patterns observed in plasma samples from PD patients with those observed in plasma and CSF of 18 patients with Dementia with Lewy Bodies (DLB) and 5 control samples. The results of the study showed considerable differences in the glycosylation profiles between PD patients and control subjects, with the majority of differential glycan groups showing decreased levels, indicating a possible disruption of glycosylation pathways in PD. More precisely, of the 10 glycan peaks (GPs) showing significantly different levels, 3 exhibited increased and 7 decreased values in plasma of PD patients. The increased glycan groups included the GP8, GP15 and GP35 peaks, while GP2, GP6, GP7, GP9, GP13, GP20 and GP22 exhibited decreased levels. A difference in glycosylation patterns was also observed between male and female probands, which is in line with previous studies in healthy individuals and patients suffering from various diseases. Altogether, we found increased representation of polysialylated and decreased representation of fucosylated N-glycans in the plasma of PD patients, a finding comparable to the results of glycosylation analyses carried out in patients with other neurodegenerative diseases. The analysis of CSF samples from DLB patients revealed correlation with PD patients in three glycan groups. In total, our findings strongly suggest that changes in glycosylation patterns may serve as the basis for the development of novel biomarkers which could be useful in early detection of individuals at risk of developing PD. Furthermore, glycan levels could also potentially be used to monitor progression of the disease, as well as in the search for putative neuroprotective treatments.

glycoprotein; Parkinson`s Disease; biomarker

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