Discordant transcriptional signatures of mitochondrial genes in Parkinson's disease human myeloid cells

Published: July 22, 2020, 7 p.m.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.20.212407v1?rss=1 Authors: Navarro, E., Udine, E., de Paiva Lopes, K., Parks, M., Riboldi, G., Schilder, B. M., Humphrey, J., Snijders, G. J. L., Vialle, R. A., Zhuang, M., Sikder, T., Argyrou, C., Allan, A., Chao, M., Farrell, K., Henderson, B., Simon, S., Raymond, D., Elango, S., Ortega, R. A., Shanker, V., Swan, M., Zhu, C., Ramdhani, R., Walker, R. H., Tse, W., Sano, M., Pereira, A. C., Ahfeldt, T., Goate, A. M., Bressman, S., Crary, J. F., de Witte, L., Frucht, S., Saunders-Pullman, R., Raj, T. Abstract: An increasing number of identified Parkinson's disease (PD) risk loci contain genes highly expressed in innate immune cells, yet their potential role in pathological mechanisms is not obvious. We have generated transcriptomic profiles of CD14+ monocytes from 230 individuals with sporadic PD and age-matched healthy subjects. We identified dysregulation of genes involved in mitochondrial and proteasomal function. We also generated transcriptomic profiles of primary microglia from autopsied brains of 55 PD and control subjects and observed discordant transcriptomic signatures of mitochondrial genes in PD monocytes and microglia. We further identified PD susceptibility genes, whose expression, relative to each risk allele, is altered in monocytes. These findings reveal that transcriptomic mitochondrial alterations are detectable in PD monocytes and are distinct from brain microglia, and facilitates efforts to understand the roles of myeloid cells in PD. Copy rights belong to original authors. Visit the link for more info