Dataset Information

Discovery and verification of panels of T-lymphocyte proteins as biomarkers of Parkinson's disease.

ABSTRACT: The diagnosis of Parkinson's disease (PD) is currently based on the clinical evaluation of extrapyramidal signs with a considerable error rate. The identification of specific markers might allow PD diagnosis before the onset of classical motor symptoms. By two-dimensional electrophoresis we identified proteome alterations in T-lymphocytes of 17 control subjects and 15 PD patients. The observed changes were used to build predictive models that were verified by the leave-one-out cross-validation. We further built two functions able to stage the subjects. We chose to verify by Western blotting the identity of spots corresponding to ?-fibrinogen and transaldolase, two recurrent proteins in six out of 20 spots. ?-Fibrinogen levels are lowered in PD patients, whereas a heavy transaldolase set of isoforms was more abundant. Eventually, we identified a list of seven proteins showing different levels in early-onset with respect to late-onset PD patients.

SUBMITTER: Alberio T

PROVIDER: S-EPMC3518817 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Discovery and verification of panels of T-lymphocyte proteins as biomarkers of Parkinson's disease.

Alberio Tiziana T Pippione Agnese C AC Zibetti Maurizio M Olgiati Simone S Cecconi Daniela D Comi Cristoforo C Lopiano Leonardo L Fasano Mauro M

Scientific reports 20121211

The diagnosis of Parkinson's disease (PD) is currently based on the clinical evaluation of extrapyramidal signs with a considerable error rate. The identification of specific markers might allow PD diagnosis before the onset of classical motor symptoms. By two-dimensional electrophoresis we identified proteome alterations in T-lymphocytes of 17 control subjects and 15 PD patients. The observed changes were used to build predictive models that were verified by the leave-one-out cross-validation. ...[more]

PMID: 23233872

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Project description:Background:The identification of circulating biomarkers that closely correlate with Parkinson's Disease (PD) has failed several times in the past. Nevertheless, in this pilot study, a translational approach was conducted, allowing the evaluation of the plasma levels of two mitochondrial-related proteins, whose combination leads to a robust model with potential diagnostic value to discriminate the PD patients from matched controls. Methods:The proposed translational approach was initiated by the analysis of secretomes from cells cultured under control or well-defined oxidative stress conditions, followed by the identification of proteins related to PD pathologic mechanisms that were altered between the two states. This pipeline was further translated into the analysis of undepleted plasma samples from 28 control and 31 PD patients. Results:From the secretome analysis, several mitochondria-related proteins were found to be differentially released between control and stress conditions and to be able to distinguish the two secretomes. Similarly, two mitochondrial-related proteins were found to be significantly changed in a PD cohort compared to matched controls. Moreover, a linear discriminant model with potential diagnostic value to discriminate PD patients was obtained using the combination of these two proteins. Both proteins are associated with apoptotic mitochondrial changes, which may correspond to potential indicators of cell death. Moreover, one of these proteins, the VPS35 protein, was reported in plasma for the first time, and its quantification was only possible due to its previous identification in the secretome analysis. Conclusions:In this work, an adaptation of a translational pipeline for biomarker selection was presented and transposed to neurological diseases, in the present case Parkinson's Disease. The novelty and success of this pilot study may arise from the combination of: i) a translational research pipeline, where plasma samples are interrogated using knowledge previously obtained from the evaluation of cells' secretome under oxidative stress; ii) the combined used of statistical analysis and an informed selection of candidates based on their link with relevant disease mechanisms, and iii) the use of SWATH-MS, an untargeted MS method that allows a complete record of the analyzed samples and a targeted data extraction of the quantitative values of proteins previously identified.

Dataset Information

Discovery and verification of panels of T-lymphocyte proteins as biomarkers of Parkinson's disease.

Publications

Discovery and verification of panels of T-lymphocyte proteins as biomarkers of Parkinson's disease.

Similar Datasets

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