Transcriptomic signatures of brain regional vulnerability to Parkinson's disease.
PMID:32139796
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IF: 6.548
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Cited by: 52
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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.

Keywords

Spatial Transcriptomics
Gene Expression

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Brain
Case-Control Studies
Databases, Genetic
Disease Progression
Female
Gene Expression Profiling
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Lewy Bodies
Male
Middle Aged
Parkinson Disease
Phenotype
Risk Assessment
Risk Factors
Transcriptome
Young Adult

Authors

Keo, Arlin
Mahfouz, Ahmed
Ingrassia, Angela M T
Meneboo, Jean-Pascal
Villenet, Celine
Mutez, Eugénie
Comptdaer, Thomas
Lelieveldt, Boudewijn P F
Figeac, Martin
Chartier-Harlin, Marie-Christine
van de Berg, Wilma D J
van Hilten, Jacobus J
Reinders, Marcel J T

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