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

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

Keo, D.L. (TU Delft Pattern Recognition and Bioinformatics; Universiteit Leiden)
Dzyubachyk, Oleh (Leiden University Medical Center)
Van Der Grond, Jeroen (Leiden University Medical Center)
van Hilten, Jacobus J. (Leiden University Medical Center)
Reinders, M.J.T. (TU Delft Pattern Recognition and Bioinformatics; Universiteit Leiden)
Mahfouz, A.M.E.T.A. (TU Delft Pattern Recognition and Bioinformatics; Universiteit Leiden)

2021

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.

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

http://resolver.tudelft.nl/uuid:aa269c74-93fb-4877-98af-153aca7544f6

https://doi.org/10.3389/fnins.2021.733501

1662-4548

Frontiers in Neuroscience, 15

Institutional Repository

journal article

© 2021 D.L. Keo, Oleh Dzyubachyk, Jeroen Van Der Grond, Jacobus J. van Hilten, M.J.T. Reinders, A.M.E.T.A. Mahfouz