Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

• DOI: 10.1038/s42003-020-0804-9
• Publication Date: 2020-03-05T17:03:07Z
• Authors: Arlin Keo; Ahmed Mahfouz; Angela M. T. Ingr...; Jean-Pascal Meneboo; Celine Villenet; Eugénie Mutez; Thomas Comptdaer; Boudewijn P. F. L...; Martin Figeac; Marie-Christine C...; Wilma D. J. van d...; Jacobus J. van Hi...; Marcel J. T. Rein...
• Keywords: Lewy body; TREM2; Human brain

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 Braak stages non-neurological adults from the Allen Human Brain Atlas. Among genes that are indicative regional vulnerability, found known genetic risk factors for disease: SCARB2 , ELOVL7, SH3GL2 SNCA BAP1 and ZNF184 . Results were confirmed two datasets subjects, while patients altered expression patterns. Co-expression analysis vulnerable a module enriched associated with dopamine synthesis microglia, another related to immune system, blood-oxygen transport, endothelial cells. Both highly expressed preclinical disease. Finally, alterations these region-specific functions may contribute selective vulnerability brains.