Library
home (Home) TU Delft Repository login Login

Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

Journal Article (2020)
Author(s)

Arlin Keo (TU Delft - Electrical Engineering, Mathematics and Computer Science, Leiden University Medical Center)

Ahmed Mahfouz (TU Delft - Electrical Engineering, Mathematics and Computer Science, Leiden University Medical Center)

Angela M.T. Ingrassia (Amsterdam UMC)

Jean Pascal Meneboo (Université de Lille)

Celine Villenet (Université de Lille)

Eugénie Mutez (Université de Lille)

Thomas Comptdaer (Université de Lille)

Boudewijn P.F. Lelieveldt (Leiden University Medical Center, TU Delft - Electrical Engineering, Mathematics and Computer Science)

Marcel J.T. Reinders (TU Delft - Electrical Engineering, Mathematics and Computer Science, Leiden University Medical Center)

undefined More Authors (External organisation)

Research Group
Pattern Recognition and Bioinformatics
DOI related publication
https://doi.org/10.1038/s42003-020-0804-9 Final published version
More Info
expand_more
Publication Year
2020
Language
English
Research Group
Pattern Recognition and Bioinformatics
Issue number
1
Volume number
3
Article number
101
Downloads counter
302
Collections
Institutional Repository
Reuse Rights

Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.

Abstract

The molecular mechanisms underlying caudal-to-rostral progression of Lewy body pathology in Parkinson’s disease remain poorly understood. Here, we identified transcriptomic signatures across brain regions involved in Braak Lewy body stages in non-neurological adults from the Allen Human Brain Atlas. Among the genes that are indicative of regional vulnerability, we found known genetic risk factors for Parkinson’s disease: SCARB2, ELOVL7, SH3GL2, SNCA, BAP1, and ZNF184. Results were confirmed in two datasets of non-neurological subjects, while in two datasets of Parkinson’s disease patients we found altered expression patterns. Co-expression analysis across vulnerable regions identified a module enriched for genes associated with dopamine synthesis and microglia, and another module related to the immune system, blood-oxygen transport, and endothelial cells. Both were highly expressed in regions involved in the preclinical stages of the disease. Finally, alterations in genes underlying these region-specific functions may contribute to the selective regional vulnerability in Parkinson’s disease brains.