A splice isoform signature of Parkinson’s disease in peripheral blood
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE34287 | GEO | 2012/12/01
SECONDARY ACCESSION(S): PRJNA149951
REPOSITORIES: GEO
Similar Datasets
Project description:In these studies, we used splice variant-specific microarrays manufactured by the ExonHit company ( www.exonhit.com) on the Affymetrix platform. The goal was to identify splice isoforms whose expression is altered in whole blood of early-stage ParkinsonM-bM-^@M-^Ys disease patients compared to healthy and neurodegenerative disease controls. The study included 19 cases of ParkinsonM-bM-^@M-^Ys disease (PD) samples, 4 of multiple system atrophy (MSA), 4 progressive supranuclear palsy (PSP) and 10 healthy controls. Thirteen splice variants were confirmed in quantitative polymerase chain reactions and used to classify blinded samples from ParkinsonM-bM-^@M-^Ys disease patients and controls with 90% accuracy and 94% sensitivity. In these studies, we used splice variant-specific microarrays manufactured by the ExonHit company ( www.exonhit.com) on the Affymetrix platform. The study included 19 cases of ParkinsonM-bM-^@M-^Ys disease (PD) samples and 20 control samples including 4 cases of multiple system atrophy (MSA), 4 progressive supranuclear palsy (PSP) and 12 healthy controls. Splice isoforms differentially expressed in PD vs any other control group were identified and validated using real-time quantitative PCR on two independent sets of 33 coded and 53 blinded samples.
2012-12-01 | E-GEOD-34287 | biostudies-arrayexpress
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes. Screen serum samples from patients with Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, multisystem atrophy and controls for deregulation of serum proteins using a cytokine-array detecting 174 secreted signaling proteins.
2011-11-23 | E-GEOD-32037 | biostudies-arrayexpress
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes. Screen serum samples from patients with Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, multisystem atrophy and controls for deregulation of serum proteins using a cytokine-array detecting 174 secreted signaling proteins.
2011-11-23 | E-GEOD-32040 | biostudies-arrayexpress
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes. Screen serum samples from patients with Parkinson's disease, progressive supranuclear palsy, corticobasal syndrome, multisystem atrophy and controls for deregulation of serum proteins using a cytokine-array detecting 174 secreted signaling proteins.
2011-11-23 | E-GEOD-32039 | biostudies-arrayexpress
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes.
2011-11-23 | GSE32040 | GEO
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes.
2011-11-23 | GSE32039 | GEO
Project description:Background: Microarray technology may offer a new opportunity to gain insight into disease-specific global protein expression profiles. The present study was performed to apply a serum cytokine-array to screen for potential molecular biomarkers for Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). Methodology/Principal Findings: Serum samples were obtained from patients with clinical diagnoses of PD (n=117), MSA (n=31) and PSP/CBS (n=38) and 99 controls. Cytokine profiles of sera of patients and controls were analyzed with a semiquantitative human cytokine antibody array. In a next step, significantly altered cytokines were individually validated by immunoassays. The cytokine array revealed a significantly altered expression of 12 cytokines. Immunoassay validation confirmed a significant increase of PDGF-BB in PSP/CBS, MSA and PD and a decrease of Prolactin in PD (Kruskal-Wallis p<0.05). A multivariate analysis taking into account diagnoses anti-Parkinsonian treatment, sex and age revealed that PDGF-BB levels were influenced only by the diagnoses (p<0.001), whereas Prolactin levels were influenced only by anti-Parkinsonian treatment (p<0.001). These findings could be corroborated by a subgroup analysis in untreated patients. Conclusions/Significance: In our unbiased cytokine array screening approach we found PDGF-BB to be elevated in PSP/CBS, MSA and PD. Increased PDGF-BB levels might be of relevance in a model of molecular biomarkers for Parkinsonian syndromes.
2011-11-23 | GSE32037 | GEO
Project description:Progressive supranuclear palsy (PSP) is a neurodegenerative disorder clinically characterized by progressive postural instability, supranuclear gaze palsy, parkinsonism, and cognitive decline caused by degeneration in specific areas of the brain including globus pallidus (GP), substantia nigra, and subthalamic nucleus. However, the pathogenetic mechanism of PSP remains unclear to date. Unbiased global proteome analysis of patients’ brain samples is an important step toward understanding PSP pathogenesis, as proteins serve as workhorses and building blocks of the cell. In this study, we conducted unbiased mass spectrometry-based global proteome analysis of GP samples from 15 PSP patients, 15 Parkinson disease (PD) patients, and 15 healthy control (HC) individuals. To analyze 45 samples, we conducted 5 batches of 11-plex isobaric tandem mass tag (TMT)-based multiplexing experiments, identifying 10,231 proteins. The gene set enrichment analysis results showed that the PD pathway was the most highly enriched, followed by pathways for oxidative phosphorylation, Alzheimer disease, Huntington disease, and non-alcoholic fatty liver disease (NAFLD) when PSP was compared to HC or PD. Most of the proteins enriched in the gene set enrichment analysis were mitochondrial proteins such as cytochrome c oxidase, NADH dehydrogenase, acyl carrier protein, succinate dehydrogenase, ADP/ATP translocase, cytochrome b-c1 complex, and/or ATP synthase. Strikingly, all of the enriched mitochondrial proteins in the PD pathway were downregulated in PSP compared to both HC and PD. The subsequent Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) protein-protein interaction (PPI) analysis and the weighted gene co-expression network analysis (WGCNA) further supported that the mitochondrial proteins were the most highly enriched in PSP. This is the first global proteome analysis of human GP from PSP patients, and this study paves the way to understanding the pathogenesis mechanism of PSP.
2022-12-08 | PXD031648 | Pride
Project description:We performed a pooled CRISPRi screen (CROP-seq) and genome editing to validate 19 genetic variants prioritized from massively parallel reporter assays to screen 5,706 polymorphisms from genome-wide association studies for both Alzheimer’s disease (AD) and Progressive Supranuclear Palsy (PSP) across 11 distinct loci. This allowed us to pinpoint regulatory targets in a cell-type specific manner.
2022-07-05 | GSE207099 | GEO
Project description:Progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD) are two neurodegenerative diseases linked, at the pathologic and genetic level, to the macrutubule associated protein tau. We identified and replicated a dose-dependent effect of the risk-associated H1 haplotype on methylation levels within the region in independent datasets in blood and brain. These data reveal that the H1 haplotype increases risk for tauopathy via differential methylation, indicating a mediating role for methylation in dementia pathophysiology. We studied epigenetic changes (DNA methylation levels) in peripheral blood from patients with PSP, FTD, and unaffected controls. Analysis of genome-wide methylation patterns revealed significant differentially methylated probes in patients versus unaffected controls.
2014-06-01 | E-GEOD-53740 | biostudies-arrayexpress