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Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 3

ABSTRACT: Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Analysis of substantia nigrae from postmortem brains of 6 patients with Parkinson's disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra.

ORGANISM(S): Homo sapiens

PROVIDER: GSE20164 | GEO | 2011/01/20

SECONDARY ACCESSION(S): PRJNA129809

REPOSITORIES: GEO

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Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 2

2011-01-20 | GSE20163 | GEO

Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 3

Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Analysis of substantia nigrae from postmortem brains of 6 patients with Parkinson's disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Substantia nigra samples from 6 PD and 5 control subjects were obtained. At autopsy, brain hemispheres were frozen in liquid nitrogen and stored at -80C in the Kathleen Price Bryan Brain Bank in the Alzheimer's Disease Research Center at Duke University. Using the RNAgents kit (Promega, Madison, Wis), RNA was extracted from SN and adjacent midbrain tissues. Double-stranded complementary DNA was made with a biotinylated T7(dT)-24 primer. Twenty micrograms of biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133A microarrays. The Affymetrix .CEL files were normalized to "all probe sets" in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.

2011-01-20 | E-GEOD-20164 | biostudies-arrayexpress

Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 2

Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson's disease. Examination of substantia nigra from postmortem brains of 8 patients with Parkinson's disease (PD). The substantia nigra samples from 8 PD subjects were obtained from the Human Brain and Spinal Fluid Resource Center, VAMC, Los Angeles, CA, the Mind Unit Brain Bank at the University of Rochester, Rochester, NY, and from Dr. E. Masliah at UCSD, San Diego, CA, and 9 control subjects were obtained from the University of Rochester Alzheimer's Disease Center brain bank. The RNA was extracted using Trizol reagent (Invitrogen), DNAse treated with Qiagen DNAse, and analyzed on a bioanalyzer. The complementary RNA was fragmented and hybridized to Affymetrix human U133A arrays. The total 17 Affymetrix .CEL files were normalized to "all probe sets" in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.

2011-01-20 | E-GEOD-20163 | biostudies-arrayexpress

Systematic meta-analysis and replication of genome-wide expression studies of Parkinson's disease: 1

Project description:Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson’s disease. Snap-frozen human substantia nigras (SNs) of 16 individuals with a clinicopathological diagnosis of incidental Lewy body (ILB) disease with Lewy bodies detected in the brainstem nuclei of locus coeruleus and substantia nigra, but generally not in higher cortical regions consistent with Braak stage 3 criteria for Parkinson's disease (PD), and 17 age-, sex-, postmortem interval-, and RNA integrity number-matched controls, who were clinicopathologically within normal limits for age collected under the rapid-autopsy program of Sun Health Research Institute or by the Harvard Brain Tissue Resource Center at McLean Hospital, were used for gene expression analyses in stage 2. Protocols were approved by the Institutional Review Board of Brigham and Women’s Hospital.

2011-01-20 | GSE20159 | GEO

Systematic meta-analysis and replication of genome-wide expression studies of Parkinson’s disease: 4

2011-01-20 | GSE20314 | GEO

Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson’s disease

2011-01-20 | GSE24378 | GEO

Systematic meta-analysis and replication of genome-wide expression studies identifies molecular pathways of Parkinson’s disease

Project description:Analysis of human dopamine (DA) from postmortem brains of 8 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Human dopamine (DA) neurons from 8 PD and 9 control subjects were obtained. Double-stranded complementary DNA was made with a biotinylated T7(dT)-24 primer. Biotinylated complementary RNA was fragmented and hybridized to Affymetrix human genome U133_X3P microarrays. The Affymetrix .CEL files were normalized to “all probe sets” in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.

2011-01-20 | E-GEOD-24378 | biostudies-arrayexpress

Systematic meta-analysis and replication of genome-wide expression studies of Parkinson’s disease: 4

Project description:Analysis of substantia nigra from postmortem brains of 4 patients with Parkinson’s disease (PD). Results provide insight into the molecular processes perturbed in the PD substantia nigra. Fresh frozen tissue blocks from cerebellar hemispheres of PD patients and controls were provided by the Queens Square Brain Bank for Neurological Disorders (London, UK). Total RNA was isolated from about 500 mg fresh frozen postmortem tissue from each subject by using Trizol reagent (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's protocol and further purified using the RNeasy mini kit (Qiagen, Hilden, Germany). Quality of the extracted total RNA was assessed using an Agilent 2100 Bioanalyzer (Agilent Technologies, Boblingen, Germany). Cerebellar mRNA with the following criteria: two distinct visible peaks for 18 s and 20 s RNA with lack of multiple small peaks indicating major degradation in Agilent Bioanalyzer fluorograms and GAPDH 3′/5′ ratios smaller 5.0 and percentage present calls greater 40% for the parameter assessed by chip hybridization were hybridized on Affymetrix human U133A GeneChip Array. Sample labeling, hybridization to arrays and image scanning (Affymetrix® GeneChip® Scanner 2500, Agilent technologies, Boblingen, Germany) were performed using standard Affymetrix® protocol (Affymetrix® Expression Analysis Technical Manual) as described previously (Bonin et al, Brain Res. Mol. Brain Res. 126, 2004). The Affymetrix .CEL files were normalized to “all probe sets” in a standardized matter, and scaled to 100 by the MAS5 algorithm implemented in the Bioconductor package.

2011-01-20 | E-GEOD-20314 | biostudies-arrayexpress

System-based analyses of brain regions functionally impacted in Parkinson's disease reveals underlying causal mechanisms

Project description:Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum and cortex are functionally connected with increasing degrees of alpha-synuclein pathology in Parkinson's disease. Functional and causal pathway analysis of gene expression and proteomic alterations in these three regions revealed pathways that correlated with deposition of alpha-synuclein. Microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release and other changes were reflected across all brain regions. Importantly a subset of these changes were replicated in Parkinson's disease blood. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene gene expression changes indicating defects in translation and/or protein turnover. Our combined approach of proteomics, RNAseq and microarray analyses provides a comprehensive view of the molecular changes that accompany alpha-synculein pathology in Parkinson's disease, and may be instrumental in understanding and diagnosing Parkinson's disease progression. Substantia Nigra (3 normal, 3 PD), Striatum (6 normal, 6 PD), Cortex (5 normal, 5 PD), Cortex non-PD neurodegeneration (2 normal, 3 DLB). Note Sample X201264 was used both for Cortex normal and for Cortex nonPD normal

2014-09-01 | E-GEOD-54282 | biostudies-arrayexpress

Metabolomics of sebum reveals lipid dysregulation in Parkinson's disease

Project description:Parkinson's disease (PD) is a progressive neurodegenerative disorder, which is characterised by degeneration of distinct neuronal populations, including dopaminergic neurons of the substantia nigra. Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype. Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis. This study shows sebum can be used to identify potential biomarkers for PD.

2020-12-21 | MTBLS2266 | MetaboLights

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