PMID- 32139796 OWN - NLM STAT- MEDLINE VI - 3 IP - 1 TI - Transcriptomic signatures of brain regional vulnerability to Parkinson's disease. PG - 101 LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Commun Biol JT - Communications biology JID - 101719179 IS - 2399-3642 (Electronic) LID - 10.1038/s42003-020-0804-9 [doi] FAU - Keo, Arlin AU - Keo A AUID- ORCID: http://orcid.org/0000-0002-7501-1033 AD - Leiden Computational Biology Center, Leiden University Medical Center, Leiden, The Netherlands. AD - Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands. FAU - Mahfouz, Ahmed AU - Mahfouz A AUID- ORCID: http://orcid.org/0000-0001-8601-2149 AD - Leiden Computational Biology Center, Leiden University Medical Center, Leiden, The Netherlands. AD - Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands. FAU - Ingrassia, Angela M T AU - Ingrassia AMT AD - Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands. FAU - Meneboo, Jean-Pascal AU - Meneboo JP AD - University Lille, Plate-forme de génomique fonctionnelle et Structurale, F-59000, Lille, France. AD - University lille. Bilille, F-59000, Lille, France. FAU - Villenet, Celine AU - Villenet C AD - University Lille, Plate-forme de génomique fonctionnelle et Structurale, F-59000, Lille, France. FAU - Mutez, Eugénie AU - Mutez E AD - University Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France. AD - Inserm, UMR-S 1172, Early Stages of Parkinson's Disease, F-59000, Lille, France. AD - University Lille, Service de Neurologie et Pathologie du mouvement, centre expert Parkinson, F-59000, Lille, France. FAU - Comptdaer, Thomas AU - Comptdaer T AUID- ORCID: http://orcid.org/0000-0002-8556-7377 AD - University Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France. AD - Inserm, UMR-S 1172, Early Stages of Parkinson's Disease, F-59000, Lille, France. FAU - Lelieveldt, Boudewijn P F AU - Lelieveldt BPF AD - Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands. AD - Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands. FAU - Figeac, Martin AU - Figeac M AD - University Lille, Plate-forme de génomique fonctionnelle et Structurale, F-59000, Lille, France. AD - University lille. Bilille, F-59000, Lille, France. FAU - Chartier-Harlin, Marie-Christine AU - Chartier-Harlin MC AUID- ORCID: http://orcid.org/0000-0001-6416-6526 AD - University Lille, Inserm, CHU Lille, UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, F-59000, Lille, France. marie-christine.chartier-harlin@inserm.fr. AD - Inserm, UMR-S 1172, Early Stages of Parkinson's Disease, F-59000, Lille, France. marie-christine.chartier-harlin@inserm.fr. FAU - van de Berg, Wilma D J AU - van de Berg WDJ AUID- ORCID: http://orcid.org/0000-0002-6175-5357 AD - Department of Anatomy and Neurosciences, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands. wdj.vandeberg@amsterdamumc.nl. FAU - van Hilten, Jacobus J AU - van Hilten JJ AUID- ORCID: http://orcid.org/0000-0002-7030-0362 AD - Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. j.j.van_hilten@lumc.nl. FAU - Reinders, Marcel J T AU - Reinders MJT AUID- ORCID: http://orcid.org/0000-0002-1148-1562 AD - Leiden Computational Biology Center, Leiden University Medical Center, Leiden, The Netherlands. m.j.t.reinders@tudelft.nl. AD - Delft Bioinformatics Lab, Delft University of Technology, Delft, The Netherlands. m.j.t.reinders@tudelft.nl. IS - 2399-3642 (Linking) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Brain/*pathology MH - Case-Control Studies MH - Databases, Genetic MH - Disease Progression MH - Female MH - *Gene Expression Profiling MH - Genetic Association Studies MH - Genetic Predisposition to Disease MH - Humans MH - Lewy Bodies/*genetics/*pathology MH - Male MH - Middle Aged MH - Parkinson Disease/*genetics/*pathology MH - Phenotype MH - Risk Assessment MH - Risk Factors MH - *Transcriptome MH - Young Adult PMC - PMC7058608 DCOM- 20210614 LR - 20210614 DP - 20200305 DEP - 20200305 AB - 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.