Dataset Information

LC-MS/MS glycomics of idiopathic rapid eye movement sleep behavior disorder.

ABSTRACT: Idiopathic REM sleep behavior disorder (iRBD) is now considered a prodromal stage of an ?-synucleinopathy-related to neurodegenerative disease such as Parkinson's diseases. Emerging evidence has shown that post-translational modification or glycosylation are implicated in dynamic disease mechanisms and the onset of many pathological conditions. We hypothesized that the characterization of the glycosylation pattern of patients with RBD would be of great value to understand the pathophysiology and underlying mechanisms and represent potentially useful biomarkers for disease-associated molecular changes. To test this hypothesis, we assessed the serum glycome of patients with RBD and compared to that of healthy controls. NanoRPLC-MS was used to generate quantitative N-glycan profiles while high-temperature PGC-LC-MS platform was employed to generate quantitative isomeric N-glycan profiles. By analyzing permethylated glycans derived from human blood sera on C18-LC-MS/MS, we identified 59 N-glycan structures in healthy (control) cohort, 56 N-glycans in RBD cohort. Sixteen N-glycans structures were found to be significantly altered in the RBD cohort (p < 0.05). N-glycans with the composition of HexNAc4 Hex5 Fuc1 , HexNAc5 Hex5 , and HexNAc4 Hex5 Fuc1 NeuAc1 presented the most substantial difference between controls and RBD patients (p < 0.01). HexNAc4 Hex5 Fuc1 NeuAc1 showed a relatively high abundance (3.1 ± 0.7% in the control cohort versus 4 ± 3% in the idiopathic RBD cohort). These N-glycans can be potential diagnostic biomarker candidates and provide a window into underlying neurodegenerative processes in patients with idiopathic RBD. In addition, 7 N-glycan isomers were significantly different between controls and RBD patients (p < 0.05). HexNAc4 Hex5 Fuc1 NeuAc1 (4511-2) and HexNAc4 Hex5 Fuc1 NeuAc2 (4512-2) showed the most substantial difference between the control and idiopathic RBD cohorts (p < 0.001). Levels of both these two isomeric structures were higher in the idiopathic RBD cohort. Further larger studies are required to assess the reproducibility of these findings and to elucidate the role played by the changes in glycan structures in the pathogenetic mechanisms of RBD. This information will be instrumental in developing molecular therapeutic targets to promote neuroprotection and prevention of neurodegeneration.

SUBMITTER: Dong X

PROVIDER: S-EPMC6625764 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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LC-MS/MS glycomics of idiopathic rapid eye movement sleep behavior disorder.

Dong Xue X Mondello Stefania S Kobeissy Firas F Talih Farid F Ferri Raffaele R Mechref Yehia Y

Electrophoresis 20180912 24

Idiopathic REM sleep behavior disorder (iRBD) is now considered a prodromal stage of an α-synucleinopathy-related to neurodegenerative disease such as Parkinson's diseases. Emerging evidence has shown that post-translational modification or glycosylation are implicated in dynamic disease mechanisms and the onset of many pathological conditions. We hypothesized that the characterization of the glycosylation pattern of patients with RBD would be of great value to understand the pathophysiology and ...[more]

PMID: 30168606

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Project description:Idiopathic rapid eye movement sleep behavior disorder (iRBD) is often a precursor to neurodegenerative disease. However, voxel-based morphological studies evaluating structural abnormalities in the brains of iRBD patients are relatively rare. This study aimed to explore cerebral structural alterations using magnetic resonance imaging and to determine their association with clinical parameters in iRBD patients. Brain structural T1-weighted MRI scans were acquired from 19 polysomnogram-confirmed iRBD patients (male:female 16:3; mean age 66.6 ± 7.0 years) and 20 age-matched healthy controls (male:female 5:15; mean age 63.7 ± 5.9 years). Gray matter volume (GMV) data were analyzed based on Statistical Parametric Mapping 8, using a voxel-based morphometry method and two-sample t-test and multiple regression analysis. Compared with controls, iRBD patients had increased GMV in the middle temporal gyrus and cerebellar posterior lobe, but decreased GMV in the Rolandic operculum, postcentral gyrus, insular lobe, cingulate gyrus, precuneus, rectus gyrus, and superior frontal gyrus. iRBD duration was positively correlated with GMV in the precuneus, cuneus, superior parietal gyrus, postcentral gyrus, posterior cingulate gyrus, hippocampus, lingual gyrus, middle occipital gyrus, middle temporal gyrus, and cerebellum posterior lobe. Furthermore, phasic chin electromyographic activity was positively correlated with GMV in the hippocampus, precuneus, fusiform gyrus, precentral gyrus, superior frontal gyrus, cuneus, inferior parietal lobule, angular gyrus, superior parietal gyrus, paracentral lobule, and cerebellar posterior lobe. There were no significant negative correlations of brain GMV with disease duration or electromyographic activity in iRBD patients. These findings expand the spectrum of known gray matter modifications in iRBD patients and provide evidence of a correlation between brain dysfunction and clinical manifestations in such patients. The protocol was approved by the Ethics Committee of Huashan Hospital (approval No. KY2013-336) on January 6, 2014. This trial was registered in the ISRCTN registry (ISRCTN18238599).

Project description:BackgroundIncreasing evidence connects the gut microbiota and the onset and/or phenotype of Parkinson's disease (PD). Differences in the abundances of specific bacterial taxa have been reported in PD patients. It is, however, unknown whether these differences can be observed in individuals at high risk, for example, with idiopathic rapid eye movement sleep behavior disorder, a prodromal condition of α-synuclein aggregation disorders including PD.ObjectivesTo compare microbiota in carefully preserved nasal wash and stool samples of subjects with idiopathic rapid eye movement sleep behavior disorder, manifest PD, and healthy individuals.MethodsMicrobiota of flash-frozen stool and nasal wash samples from 76 PD patients, 21 idiopathic rapid eye movement sleep behavior disorder patients, and 78 healthy controls were assessed by 16S and 18S ribosomal RNA amplicon sequencing. Seventy variables, related to demographics, clinical parameters including nonmotor symptoms, and sample processing, were analyzed in relation to microbiome variability and controlled differential analyses were performed.ResultsDifferentially abundant gut microbes, such as Akkermansia, were observed in PD, but no strong differences in nasal microbiota. Eighty percent of the differential gut microbes in PD versus healthy controls showed similar trends in idiopathic rapid eye movement sleep behavior disorder, for example, Anaerotruncus and several Bacteroides spp., and correlated with nonmotor symptoms. Metagenomic sequencing of select samples enabled the reconstruction of genomes of so far uncharacterized differentially abundant organisms.ConclusionOur study reveals differential abundances of gut microbial taxa in PD and its prodrome idiopathic rapid eye movement sleep behavior disorder in comparison to the healthy controls, and highlights the potential of metagenomics to identify and characterize microbial taxa, which are enriched or depleted in PD and/or idiopathic rapid eye movement sleep behavior disorder. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Dataset Information

LC-MS/MS glycomics of idiopathic rapid eye movement sleep behavior disorder.

Publications

LC-MS/MS glycomics of idiopathic rapid eye movement sleep behavior disorder.

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