Transcriptomic signatures of brain regional vulnerability to Parkinson's disease.

Communications Biology
Arlin KeoMarcel J T Reinders

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.

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Citations

Oct 7, 2020·International Journal of Molecular Sciences·Ashley HallKimberley J Billingsley
Dec 29, 2020·Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging·Magdalena MroczekWadid Sirry
Jan 12, 2021·Nature Protocols·Nicola FattorelliRenzo Mancuso
Mar 2, 2021·Neurobiology of Stress·Mandy MeijerAhmed Mahfouz
Mar 11, 2021·Environmental Pollution·B SubediD R Hammond-Weinberger
Mar 9, 2021·Journal of Parkinson's Disease·Tiago A MestreConnie Marras
May 18, 2021·Frontiers in Neuroanatomy·Ilaria BalboEriola Hoxha
May 8, 2021·The European Journal of Neuroscience·Angeliki Zarkali, Rimona S Weil
Sep 10, 2021·Antioxidants & Redox Signaling·Elise MalardLaurent Chatre

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Datasets Mentioned

BETA
GSE49036

Methods Mentioned

BETA
spatial transcriptomics
RNA-seq
RNAseq

Software Mentioned

TopHat
Ensembl
hgu133plus2
DAVID
DisGeNET
DESeq2 package
dynamicTreeCut R - package
- package
biomaRt R - package
R

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