Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of human patients with Parkinsons disease (50), 33 patients with neurodegenerative diseases other than PD, and 23 healthy controls

ABSTRACT: Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular marker here identified is strongly associated with risk of PD in 66 samples of the training set (third tertile cross-validated odds ratio of 5.7 {P for trend 0.005}). It is further validated in 39 independent test samples (third tertile odds ratio of 5.1 {P for trend 0.04}). The genes differentially expressed in patients with PD, or Alzheimer's or progressive supranuclear palsy offer unique insights into disease-linked processes detectable in peripheral blood. Combining gene expression scans in blood and linked clinical data will facilitate the rapid characterization of candidate biomarkers as demonstrated here with respect to PD. Experiment Overall Design: Whole blood expression data from 50 patients with Parkinson's disease, 33 with neurodegenerative diseases other than PD, and 23 healthy controls.

ORGANISM(S): Homo sapiens

SUBMITTER: Aron Eklund

PROVIDER: E-GEOD-6613 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular markers of early Parkinson's disease based on gene expression in blood.

Scherzer Clemens R CR Eklund Aron C AC Morse Lee J LJ Liao Zhixiang Z Locascio Joseph J JJ Fefer Daniel D Schwarzschild Michael A MA Schlossmacher Michael G MG Hauser Michael A MA Vance Jeffery M JM Sudarsky Lewis R LR Standaert David G DG Growdon John H JH Jensen Roderick V RV Gullans Steven R SR

Proceedings of the National Academy of Sciences of the United States of America 20070110 3

Parkinson's disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular multigene marker here identified is associated with risk of PD in 66 samples of the training set comprising ...[more]

PMID: 17215369

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Project description:Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. We study changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls (Discovery set?) by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. By applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays, gene expression profiling discriminates patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts were validated by RT-qPCR in an independent cohort of 12 patients and controls (?Validation set). Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention. Analyzed samples include blood samples from 40 PD patients and 20 healthy controls. Of the original 60 samples, one (a control sample) did not pass the microarray hybridization quality controls and was excluded from further analyses. All results of bioinformatics analyses shown in this study refer to this set of 59 samples (reported here).

Dataset Information

Transcription profiling of human patients with Parkinsons disease (50), 33 patients with neurodegenerative diseases other than PD, and 23 healthy controls

Publications

Molecular markers of early Parkinson's disease based on gene expression in blood.

Similar Datasets

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