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Blood transcriptomic signatures associated with molecular changes in the brain and clinical outcomes in Parkinson’s disease

Author

Listed:
  • Krithi Irmady

    (The Rockefeller University)

  • Caryn R. Hale

    (The Rockefeller University)

  • Rizwana Qadri

    (The Rockefeller University)

  • John Fak

    (The Rockefeller University)

  • Sitsandziwe Simelane

    (The Rockefeller University)

  • Thomas Carroll

    (The Rockefeller University)

  • Serge Przedborski

    (Columbia University
    Columbia University
    Columbia University)

  • Robert B. Darnell

    (The Rockefeller University
    The Rockefeller University)

Abstract

The ability to use blood to predict the outcomes of Parkinson’s disease, including disease progression and cognitive and motor complications, would be of significant clinical value. We undertook bulk RNA sequencing from the caudate and putamen of postmortem Parkinson’s disease (n = 35) and control (n = 40) striatum, and compared molecular profiles with clinical features and bulk RNA sequencing data obtained from antemortem peripheral blood. Cognitive and motor complications of Parkinson’s disease were associated with molecular changes in the caudate (stress response) and putamen (endothelial pathways) respectively. Later and earlier-onset Parkinson’s disease were molecularly distinct, and disease duration was associated with changes in caudate (oligodendrocyte development) and putamen (cellular senescence), respectively. Transcriptome patterns in the postmortem Parkinson’s disease brain were also evident in antemortem peripheral blood, and correlated with clinical features of the disease. Together, these findings identify molecular signatures in Parkinson’s disease patients’ brain and blood of potential pathophysiologic and prognostic importance.

Suggested Citation

  • Krithi Irmady & Caryn R. Hale & Rizwana Qadri & John Fak & Sitsandziwe Simelane & Thomas Carroll & Serge Przedborski & Robert B. Darnell, 2023. "Blood transcriptomic signatures associated with molecular changes in the brain and clinical outcomes in Parkinson’s disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39652-6
    DOI: 10.1038/s41467-023-39652-6
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    References listed on IDEAS

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    1. Tyler J. Bussian & Asef Aziz & Charlton F. Meyer & Barbara L. Swenson & Jan M. van Deursen & Darren J. Baker, 2018. "Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline," Nature, Nature, vol. 562(7728), pages 578-582, October.
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