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Article Dans Une Revue Communications Biology Année : 2020

Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

Résumé

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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Dates et versions

hal-04335973 , version 1 (25-01-2024)

Identifiants

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Arlin Keo, Ahmed Mahfouz, Angela Ingrassia, Jean-Pascal Meneboo, Celine Villenet, et al.. Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease. Communications Biology, 2020, 3 (1), pp.101. ⟨10.1038/s42003-020-0804-9⟩. ⟨hal-04335973⟩
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