Open AccessTranscriptional network analysis in frontal cortex in L ewy body diseases with focus on dementia with L ewy bodies
Author(s) -
Santpere Gabriel,
GarciaEsparcia Paula,
AndresBenito Pol,
LorenteGaldos Belen,
Navarro Arcadi,
Ferrer Isidro
Publication year - 2018
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12511
Subject(s) - biology , gene , dementia with lewy bodies , neuroscience , gene expression , dementia , microbiology and biotechnology , disease , genetics , medicine , pathology
The present study investigates global transcriptional changes in frontal cortex area 8 in incidental Lewy Body disease (iLBD), Parkinson disease (PD) and Dementia with Lewy bodies (DLB). We identified different coexpressed gene sets associated with disease stages, and gene ontology categories enriched in gene modules and differentially expressed genes including modules or gene clusters correlated to iLBD comprising upregulated dynein genes and taste receptors, and downregulated innate inflammation. Focusing on DLB, we found modules with genes significantly enriched in functions related to RNA and DNA production, mitochondria and energy metabolism, purine metabolism, chaperone and protein folding system and synapses and neurotransmission (particularly the GABAergic system). The expression of more than fifty selected genes was assessed with real time quantitative polymerase chain reaction. Our findings provide, for the first time, evidence of molecular cortical alterations in iLBD and involvement of several key metabolic pathways and gene hubs in DLB which may underlie cognitive impairment and dementia.