A network approach to diagnostic biomarkers in progressive supranuclear palsy

Authors

  • Jose A. Santiago MS,

    1. Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA
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  • Judith A. Potashkin PhD

    Corresponding author
    1. Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA
    • Correspondence to: Judith A. Potashkin, Department of Cellular and Molecular Pharmacology, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Rd., North Chicago, IL 60064-3037, USA; judy.potashkin@rosalindfranklin.edu

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  • Funding agencies: This study was supported by US Army Medical Research and Materiel Command under awards number W81XWH-09-0708 and by Splice Variant Risk Markers for PSP, grant 507-12, from the CurePSP- Foundation for PSP, CBD and Related Brain Diseases (to J.A.P.). The funding agency had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the online version of this article.

ABSTRACT

Diagnosis of progressive supranuclear palsy (PSP) remains challenging because of the clinical overlap with Parkinson's disease (PD). To date, disease-specific biomarkers have yet to be identified. In the absence of reliable biomarkers, we used an integrated network approach to identify genes and related biological pathways associated with PSP. We tested a highly ranked gene in cellular whole-blood samples from 122 patients enrolled in the Prognostic Biomarker Study. Biological and functional analysis identified 13 modules related to activation of leukocytes and lymphocytes, protein dephosphorylation, and phosphatase activity. Integration of these results with those from microarrays identified ptpn1 as a potential biomarker for PSP. Assessment of biomarker performance revealed that ptpn1 could be used to distinguish PSP patients from PD patients with 86% diagnostic accuracy. Ptpn1 may be a diagnostic marker useful for distinguishing PSP and PD. Further evaluation in a larger well-characterized prospective study is warranted. © 2013 International Parkinson and Movement Disorder Society

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