TY - JOUR
T1 - Transcriptomic signatures of brain regional vulnerability to Parkinson's disease
AU - Keo, Arlin
AU - Mahfouz, Ahmed
AU - Ingrassia, Angela M.T.
AU - Meneboo, Jean Pascal
AU - Villenet, Celine
AU - Mutez, Eugénie
AU - Comptdaer, Thomas
AU - Lelieveldt, Boudewijn P.F.
AU - Figeac, Martin
AU - Chartier-Harlin, Marie Christine
AU - van de Berg, Wilma D.J.
AU - van Hilten, Jacobus J.
AU - Reinders, Marcel J.T.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85081308526&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s42003-020-0804-9
DO - https://doi.org/10.1038/s42003-020-0804-9
M3 - Article
C2 - 32139796
SN - 2399-3642
VL - 3
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 101
ER -