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; Robert B Darnell

doi:10.1038/s41467-023-39652-6

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

Nat Commun. 2023 Jul 5;14(1):3956. doi: 10.1038/s41467-023-39652-6.

Authors

Krithi Irmady^#¹, Caryn R Hale^#², Rizwana Qadri², John Fak², Sitsandziwe Simelane², Thomas Carroll³, Serge Przedborski^{4

5

6}, Robert B Darnell^{7

8}

Affiliations

¹ Laboratory of Molecular Neuro-oncology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA. kirmady@rockefeller.edu.
² Laboratory of Molecular Neuro-oncology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
³ Bioinformatics Resource Center, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA.
⁴ Department of Neurology, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.
⁵ Department of Pathology & Cell Biology, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.
⁶ Department of Neuroscience, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.
⁷ Laboratory of Molecular Neuro-oncology, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA. darnelr@rockefeller.edu.
⁸ Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA. darnelr@rockefeller.edu.

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Brain / metabolism
Corpus Striatum / metabolism
Humans
Parkinson Disease* / metabolism
Putamen
Transcriptome

Abstract

Publication types

MeSH terms

Grants and funding