Transcriptomic Signatures Associated With Regional Cortical Thickness Changes in Parkinson’s Disease

D.L. Keo, Oleh Dzyubachyk, Jeroen Van Der Grond, Jacobus J. van Hilten, M.J.T. Reinders, A.M.E.T.A. Mahfouz

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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.
Original languageEnglish
Article number733501
Number of pages15
JournalFrontiers in Neuroscience
Volume15
DOIs
Publication statusPublished - 2021

Keywords

  • cortical thickness
  • gene expression analysis
  • imaging-genetics
  • neurodegenerative diseases
  • neuroimaging data

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