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Article: A Systems View of the Differences between APOE ε4 Carriers and Non-carriers in Alzheimer's Disease

TitleA Systems View of the Differences between APOE ε4 Carriers and Non-carriers in Alzheimer's Disease
Authors
Issue Date2016
PublisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/aging_neuroscience
Citation
Frontiers in Aging Neuroscience, 2016, v. 8, p. 171 How to Cite?
AbstractAPOE ε4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and accounts for 50-65% of late-onset AD. Late-onset AD patients carrying or not carrying APOE ε4 manifest many clinico-pathological distinctions. Thus, we applied a weighted gene co-expression network analysis to identify specific co-expression modules in AD based on APOE ε4 stratification. Two specific modules were identified in AD APOE ε4 carriers and one module was identified in non-carriers. The hub genes of one module of AD APOE ε4 carriers were ISOC1, ENO3, GDF10, GNB3, XPO4, ACLY and MATN2. The other module of AD APOE ε4 carriers consisted of 10 hub genes including ANO3, ARPP21, HPCA, RASD2, PCP4 and ADORA2A. The module of AD APOE ε4 non-carriers consisted of 16 hub genes including DUSP5, TNFRSF18, ZNF331, DNAJB5 and RIN1. The module of AD APOE ε4 carriers including ISOC1 and ENO3 and the module of non-carriers contained the most highly connected hub gene clusters. mRNA expression of the genes in the cluster of the ISOC1 and ENO3 module of carriers was shown to be correlated in a time-dependent manner under APOE ε4 treatment but not under APOE ε3 treatment. In contrast, mRNA expression of the genes in the cluster of non-carriers' module was correlated under APOE ε3 treatment but not under APOE ε4 treatment. The modules of carriers demonstrated genetic bases and were mainly enriched in hereditary disorders and neurological diseases, energy metabolism-associated signaling and G protein-coupled receptor-associated pathways. The module including ISOC1 and ENO3 harbored two conserved promoter motifs in its hub gene cluster that could be regulated by common transcription factors and miRNAs. The module of non-carriers was mainly enriched in neurological, immunological and cardiovascular diseases and was correlated with Parkinson's disease. These data demonstrate that AD in APOE ε4 carriers involves more genetic factors and particular biological processes, whereas AD in APOE ε4 non-carriers shares more common pathways with other types of diseases. The study reveals differential genetic bases and pathogenic and pathological processes between carriers and non-carriers, providing new insight into the mechanisms of the differences between APOE ε4 carriers and non-carriers in AD.
Persistent Identifierhttp://hdl.handle.net/10722/248490
ISSN
2017 Impact Factor: 3.582
2015 SCImago Journal Rankings: 1.808
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJiang S, S-
dc.contributor.authorTang, L-
dc.contributor.authorZhao, N-
dc.contributor.authorYang, W-
dc.contributor.authorQiu, Y-
dc.contributor.authorChen, HZ-
dc.date.accessioned2017-10-18T08:44:01Z-
dc.date.available2017-10-18T08:44:01Z-
dc.date.issued2016-
dc.identifier.citationFrontiers in Aging Neuroscience, 2016, v. 8, p. 171-
dc.identifier.issn1663-4365-
dc.identifier.urihttp://hdl.handle.net/10722/248490-
dc.description.abstractAPOE ε4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and accounts for 50-65% of late-onset AD. Late-onset AD patients carrying or not carrying APOE ε4 manifest many clinico-pathological distinctions. Thus, we applied a weighted gene co-expression network analysis to identify specific co-expression modules in AD based on APOE ε4 stratification. Two specific modules were identified in AD APOE ε4 carriers and one module was identified in non-carriers. The hub genes of one module of AD APOE ε4 carriers were ISOC1, ENO3, GDF10, GNB3, XPO4, ACLY and MATN2. The other module of AD APOE ε4 carriers consisted of 10 hub genes including ANO3, ARPP21, HPCA, RASD2, PCP4 and ADORA2A. The module of AD APOE ε4 non-carriers consisted of 16 hub genes including DUSP5, TNFRSF18, ZNF331, DNAJB5 and RIN1. The module of AD APOE ε4 carriers including ISOC1 and ENO3 and the module of non-carriers contained the most highly connected hub gene clusters. mRNA expression of the genes in the cluster of the ISOC1 and ENO3 module of carriers was shown to be correlated in a time-dependent manner under APOE ε4 treatment but not under APOE ε3 treatment. In contrast, mRNA expression of the genes in the cluster of non-carriers' module was correlated under APOE ε3 treatment but not under APOE ε4 treatment. The modules of carriers demonstrated genetic bases and were mainly enriched in hereditary disorders and neurological diseases, energy metabolism-associated signaling and G protein-coupled receptor-associated pathways. The module including ISOC1 and ENO3 harbored two conserved promoter motifs in its hub gene cluster that could be regulated by common transcription factors and miRNAs. The module of non-carriers was mainly enriched in neurological, immunological and cardiovascular diseases and was correlated with Parkinson's disease. These data demonstrate that AD in APOE ε4 carriers involves more genetic factors and particular biological processes, whereas AD in APOE ε4 non-carriers shares more common pathways with other types of diseases. The study reveals differential genetic bases and pathogenic and pathological processes between carriers and non-carriers, providing new insight into the mechanisms of the differences between APOE ε4 carriers and non-carriers in AD.-
dc.languageeng-
dc.publisherFrontiers Research Foundation. The Journal's web site is located at http://www.frontiersin.org/aging_neuroscience-
dc.relation.ispartofFrontiers in Aging Neuroscience-
dc.rightsThis Document is Protected by copyright and was first published by Frontiers. All rights reserved. It is reproduced with permission.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleA Systems View of the Differences between APOE ε4 Carriers and Non-carriers in Alzheimer's Disease-
dc.typeArticle-
dc.identifier.emailYang, W: yangwl@hkucc.hku.hk-
dc.identifier.authorityYang, W=rp00524-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3389/fnagi.2016.00171-
dc.identifier.hkuros280956-
dc.identifier.volume8-
dc.identifier.spage171-
dc.identifier.epage171-
dc.identifier.isiWOS:000379392400001-
dc.publisher.placeSwitzerland-

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