Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

Keo, A.; Mahfouz, A.; Ingrassia, A.M.T.; Meneboo, J.P.; Villenet, C.; Mutez, E.; ... ; Reinders, M.J.T. (2022)

Article / Letter to editor

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.

• All authors: Keo, A.; Mahfouz, A.; Ingrassia, A.M.T.; Meneboo, J.P.; Villenet, C.; Mutez, E.; Comptdaer, T.; Lelieveldt, B.P.F.; Figeac, M.; Chartier-Harlin, M.C.; Berg, W.D.J. van de; Hilten, J.J. van; Reinders, M.J.T.
• Date: 2022-03-05
• Journal: Communications Biology
• Volume: 3
• DOI: doi:10.1038/s42003-020-0804-9
• Link: https://www.nature.com/articles/s42003-020-0804-9