TY - JOUR
T1 - Dysregulation of mitochondrial and proteolysosomal genes in Parkinson’s disease myeloid cells
AU - Navarro, Elisa
AU - Udine, Evan
AU - Lopes, Katia de Paiva
AU - Parks, Madison
AU - Riboldi, Giulietta
AU - Schilder, Brian M.
AU - Humphrey, Jack
AU - Snijders, Gijsje J.L.
AU - Vialle, Ricardo A.
AU - Zhuang, Maojuan
AU - Sikder, Tamjeed
AU - Argyrou, Charalambos
AU - Allan, Amanda
AU - Chao, Michael J.
AU - Farrell, Kurt
AU - Henderson, Brooklyn
AU - Simon, Sarah
AU - Raymond, Deborah
AU - Elango, Sonya
AU - Ortega, Roberto A.
AU - Shanker, Vicki
AU - Swan, Matthew
AU - Zhu, Carolyn W.
AU - Ramdhani, Ritesh
AU - Walker, Ruth H.
AU - Tse, Winona
AU - Sano, Mary
AU - Pereira, Ana C.
AU - Ahfeldt, Tim
AU - Goate, Alison M.
AU - Bressman, Susan
AU - Crary, John F.
AU - de Witte, Lotje
AU - Frucht, Steven
AU - Saunders-Pullman, Rachel
AU - Raj, Towfique
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/9
Y1 - 2021/9
N2 - An increasing number of identified Parkinson’s disease (PD) risk loci contain genes highly expressed in innate immune cells, yet their role in pathology is not understood. We hypothesized that PD susceptibility genes modulate disease risk by influencing gene expression within immune cells. To address this, we generated transcriptomic profiles of monocytes from healthy subjects and 230 individuals with sporadic PD. We observed dysregulation of mitochondrial and proteasomal pathways. We also generated transcriptomic profiles of primary microglia from brains of 55 subjects and observed discordant transcriptomic signatures of mitochondrial genes in PD monocytes and microglia. We further identified 17 PD susceptibility genes whose expression, relative to each risk allele, was altered in monocytes. These findings reveal widespread transcriptomic alterations in PD monocytes, with some being distinct from microglia, and facilitate efforts to understand the roles of myeloid cells in PD as well as the development of biomarkers.
AB - An increasing number of identified Parkinson’s disease (PD) risk loci contain genes highly expressed in innate immune cells, yet their role in pathology is not understood. We hypothesized that PD susceptibility genes modulate disease risk by influencing gene expression within immune cells. To address this, we generated transcriptomic profiles of monocytes from healthy subjects and 230 individuals with sporadic PD. We observed dysregulation of mitochondrial and proteasomal pathways. We also generated transcriptomic profiles of primary microglia from brains of 55 subjects and observed discordant transcriptomic signatures of mitochondrial genes in PD monocytes and microglia. We further identified 17 PD susceptibility genes whose expression, relative to each risk allele, was altered in monocytes. These findings reveal widespread transcriptomic alterations in PD monocytes, with some being distinct from microglia, and facilitate efforts to understand the roles of myeloid cells in PD as well as the development of biomarkers.
UR - http://www.scopus.com/inward/record.url?scp=85121661114&partnerID=8YFLogxK
U2 - 10.1038/s43587-021-00110-x
DO - 10.1038/s43587-021-00110-x
M3 - Article
AN - SCOPUS:85121661114
SN - 2662-8465
VL - 1
SP - 850
EP - 863
JO - Nature Aging
JF - Nature Aging
IS - 9
ER -