PT  - JOURNAL ARTICLE
AU  - Arlin Keo
AU  - Ahmed Mahfouz
AU  - Angela M.T. Ingrassia
AU  - Jean-Pascal Meneboo
AU  - Celine Villenet
AU  - Eugénie Mutez
AU  - Thomas Comptdaer
AU  - Boudewijn P.F. Lelieveldt
AU  - Martin Figeac
AU  - Marie-Christine Chartier-Harlin
AU  - Wilma D.J. van de Berg
AU  - Jacobus J. van Hilten
AU  - Marcel J.T. Reinders
TI  - Transcriptomic signatures of brain regional vulnerability to Parkinson’s disease
AID  - 10.1101/664771
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 664771
4099  - http://biorxiv.org/content/early/2019/06/10/664771.short
4100  - http://biorxiv.org/content/early/2019/06/10/664771.full
AB  - The molecular mechanisms underlying the caudal-to-rostral progression of Lewy body pathology in Parkinson’s disease (PD) remains poorly understood. Here, we aimed to unravel transcriptomic signatures across brain regions involved in Braak Lewy body stages in non-neurological controls and PD donors. Using human postmortem brain datasets of non-neurological adults from the Allen Human Brain Atlas, we identified expression patterns related to PD progression, including genes found in PD genome-wide associations studies: SNCA, ZNF184, BAP1, SH3GL2, ELOVL7, and SCARB2. We confirmed these patterns in two datasets of non-neurological subjects (Genotype-Tissue Expression project and UK Brain Expression Consortium) and found altered patterns in two datasets of PD patients. Additionally, co-expression analysis across vulnerable regions identified two modules associated with dopamine synthesis, the motor and immune system, blood-oxygen transport, and contained microglial and endothelial cell markers, respectively. Alterations in genes underlying these region-specific functions may contribute to the selective regional vulnerability in PD brains.