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Transcriptomic signatures associated with regional cortical thickness changes in Parkinson’s disease

View ORCID ProfileArlin Keo, View ORCID ProfileOleh Dzyubachyk, View ORCID ProfileJeroen van der Grond, View ORCID ProfileJacobus J. van Hilten, View ORCID ProfileMarcel J. T. Reinders, View ORCID ProfileAhmed Mahfouz
doi: https://doi.org/10.1101/2020.06.19.158808
Arlin Keo
1Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands
2Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands
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  • For correspondence: arlinkeo@gmail.com
Oleh Dzyubachyk
3Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
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Jeroen van der Grond
3Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
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Jacobus J. van Hilten
4Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands
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Marcel J. T. Reinders
1Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands
2Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands
5Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
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Ahmed Mahfouz
1Leiden Computational Biology Center, Leiden University Medical Center, Leiden, the Netherlands
2Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands
5Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands
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Abstract

Cortical atrophy is a common manifestation in Parkinson’s disease, particularly in later disease stages. Here, we investigated patterns of cortical thickness using T1-weighted anatomical MRI data of 149 Parkinson’s disease patients and 369 controls. To elucidate the molecular underpinnings of cortical thickness changes in Parkinson’s disease, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and neuroimaging features. For this purpose, we used partial least squares regression to identify gene expression patterns correlated with cortical thickness changes. In addition, we identified gene expression patterns underlying the relationship between cortical thickness and clinical domains of Parkinson’s disease. Our results show that genes whose expression in the healthy brain is associated with cortical thickness changes in Parkinson’s disease are enriched in biological pathways related to sumoylation, regulation of mitotic cell cycle, mitochondrial translation, DNA damage responses, and ER-Golgi traffic. The associated pathways were highly related to each other and all belong to cellular maintenance mechanisms. The expression of genes within most pathways was negatively correlated with cortical thickness changes, showing higher expression in regions associated with decreased cortical thickness (atrophy). On the other hand, sumoylation pathways were positively correlated with cortical thickness changes, showing higher expression in regions with increased cortical thickness (hypertrophy). Our findings suggest that alterations in the balanced interplay of these mechanisms play a role in changes of cortical thickness in Parkinson’s disease and possibly influence motor and cognitive functions.

Competing Interest Statement

The authors have declared no competing interest.

  • Abbreviations

    AHBA
    Allen Human Brain Atlas;
    CT
    cortical thickness;
    LED
    levodopa equivalent dose;
    MDS-UPDRS
    Movement Disorder Society-sponsored revision of the unified Parkinson’s disease rating scale;
    MMSE
    mini-mental state examination;
    PLS
    partial least squares;
    SENS-PD
    severity of non-dopaminergic symptoms in Parkinson’s disease
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    Posted June 19, 2020.
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    Transcriptomic signatures associated with regional cortical thickness changes in Parkinson’s disease
    Arlin Keo, Oleh Dzyubachyk, Jeroen van der Grond, Jacobus J. van Hilten, Marcel J. T. Reinders, Ahmed Mahfouz
    bioRxiv 2020.06.19.158808; doi: https://doi.org/10.1101/2020.06.19.158808
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    Transcriptomic signatures associated with regional cortical thickness changes in Parkinson’s disease
    Arlin Keo, Oleh Dzyubachyk, Jeroen van der Grond, Jacobus J. van Hilten, Marcel J. T. Reinders, Ahmed Mahfouz
    bioRxiv 2020.06.19.158808; doi: https://doi.org/10.1101/2020.06.19.158808

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