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

Krithi Irmady (), Caryn R. Hale, Rizwana Qadri, John Fak, Sitsandziwe Simelane, Thomas Carroll, Serge Przedborski and Robert B. Darnell ()
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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
Robert B. Darnell: The Rockefeller University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-39652-6

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