Transcriptomic Signatures Associated With Regional Cortical Thickness Changes in Parkinson’s Disease
Frontiers in Neuroscience, vol. 15, pp. 733501
Abstract
Cortical atrophy is a common manifestation in Parkinson's disease (PD), particularly in advanced stages of the disease. To elucidate the molecular underpinnings of cortical thickness changes in PD, we performed an integrated analysis of brain-wide healthy transcriptomic data from the Allen Human Brain Atlas and patterns of cortical thickness based on T1-weighted anatomical MRI data of 149 PD patients and 369 controls. 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 PD. Our results show that genes whose expression in the healthy brain is associated with cortical thickness changes in PD 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 PD and possibly influence motor and cognitive functions.
Authors 6
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Leiden University Medical Center · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Lab, Delft University of Technology, Delft, Netherlands
Leiden Computational Biology Center, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Radiology, Leiden University Medical Center, Leiden, Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Neurology, Leiden University Medical Center, Leiden, Netherlands
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Marcel J. T. Reinders corresponding Aachen Department of Human Genetics Leiden Computational Biology Center
Leiden University Medical Center · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Lab, Delft University of Technology, Delft, Netherlands
Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
Leiden Computational Biology Center, Leiden University Medical Center, Leiden, Netherlands
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Ahmed Essam Mahfouz corresponding Aachen Department of Human Genetics Leiden Computational Biology Center
Leiden University Medical Center · Delft University of Technology
Affiliation as printed
Delft Bioinformatics Lab, Delft University of Technology, Delft, Netherlands
Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands
Leiden Computational Biology Center, Leiden University Medical Center, Leiden, Netherlands
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