Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease

• Published in: Communications biology Vol. 3; no. 1; p. 101
• Main 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.03.2020; Nature Publishing Group
• Subjects: 38/39; 38/61; 38/91; 631/114/116; 692/617/375/1718; Adolescent; Adult; Aged; Aged, 80 and over; Biochemistry, Molecular Biology; Biology; Biomedical and Life Sciences; Brain; Brain - pathology; Case-Control Studies; Databases, Genetic; Disease Progression; Dopamine; Endothelial cells; Female; Gene Expression Profiling; Genetic Association Studies; Genetic Predisposition to Disease; Genomics; Human health and pathology; Humans; Immune system; Lewy bodies; Lewy Bodies - genetics; Lewy Bodies - pathology; Life Sciences; Male; Microglia; Middle Aged; Molecular modelling; Movement disorders; Neurobiology; Neurodegenerative diseases; Neurons and Cognition; Parkinson Disease - genetics; Parkinson Disease - pathology; Parkinson's disease; Phenotype; Risk Assessment; Risk Factors; Transcriptome; Young Adult
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-0804-9

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. Keo et al. perform a meta-analysis of region-specific transcriptomic profiles across different Braak stages. They identify genes and modules that may be involved in the selective regional vulnerability and the progression of Parkinson’s disease.