2024-03-28T14:24:12Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1644662020-12-13T09:21:13Zcom_10261_3284com_10261_1col_10261_3285
00925njm 22002777a 4500
dc
Infante, Jon
author
Prieto-Sánchez, Carlos
author
Sierra, María
author
Sánchez-Juan, Pascual
author
González-Aramburu, Isabel
author
Sánchez-Quintana, Coro
author
Berciano, José
author
Combarros, Onofre
author
Sainz, Jesús
author
2016
Patients with Parkinson's disease (PD) carrying the G2019S mutation of the LRRK2 gene provide an opportunity of studying in a homogeneous setting the molecular pathways involved in the pathogenesis of common idiopathic forms of PD. However, whether common mechanisms are involved in both conditions in not known. Here, we compared genome-wide gene expression (RNA sequencing) in peripheral blood between PD patients carrying the G2019S mutation of the LRRK2 gene and idiopathic PD cases, to deepen in the understanding of this topic. In addition, we compared the blood transcriptome between 2 cohorts of carriers of the G2019S mutation (symptomatic and asymptomatic) and 2 cohorts of noncarriers (symptomatic and asymptomatic) for detecting transcriptomic changes attributable to the presence of the G2019S mutation. We searched for gene enrichment in Reactome or Kyoto Encyclopedia of Genes and Genomes pathways. We found that despite some overlap, peripheral blood transcriptome differs widely between idiopathic and LRRK2 G2019S-associated PD, with only 4 deregulated pathways shared by both conditions (complement and coagulation cascades, cell adhesion molecules, hematopoietic cell lineage, and extracellular matrix organization). Changes in the blood transcriptome observed in asymptomatic carriers of the mutation included 6 genes known to be associated with PD in genome-wide association studies and also pathways related with immunity. Our findings emphasize the notion that PD is likely a pathogenically heterogeneous condition and suggest the existence of specific mechanisms involved in LRRK2-associated PD.
Neurobiology of Aging 38: 214.e1-214.e5 (2016)
http://hdl.handle.net/10261/164466
10.1016/j.neurobiolaging.2015.10.026
http://dx.doi.org/10.13039/501100004587
26675812
Peripheral blood
RNA-seq
Trancriptome
Gene expression
LRRK2
Parkinson's disease
Comparative blood transcriptome analysis in idiopathic and LRRK2 G2019S-associated Parkinson's disease