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dc.contributor.authorCalero, Olga 
dc.contributor.authorBullido, María J
dc.contributor.authorClarimón, Jordi
dc.contributor.authorFrank-García, Ana
dc.contributor.authorMartínez-Martín, Pablo
dc.contributor.authorLleó, Alberto
dc.contributor.authorRey, María Jesús
dc.contributor.authorSastre, Isabel
dc.contributor.authorRábano, Alberto
dc.contributor.authorPedro-Cuesta, Jesus de 
dc.contributor.authorFerrer, Isidro
dc.contributor.authorCalero, Miguel
dc.identifier.citationPLoS One. 2012;7(8):e43926.es_ES
dc.description.abstractThe β site APP cleaving enzyme 1 (BACE1) is the rate-limiting β-secretase enzyme in the amyloidogenic processing of APP and Aβ formation, and therefore it has a prominent role in Alzheimer's disease (AD) pathology. Recent evidence suggests that the prion protein (PrP) interacts directly with BACE1 regulating its β-secretase activity. Moreover, PrP has been proposed as the cellular receptor involved in the impairment of synaptic plasticity and toxicity caused by Aβ oligomers. Provided that common pathophysiologic mechanisms are shared by Alzheimer's and Creutzfeldt-Jakob (CJD) diseases, we investigated for the first time to the best of our knowledge a possible association of a common synonymous BACE1 polymorphism (rs638405) with sporadic CJD (sCJD). Our results indicate that BACE1 C-allele is associated with an increased risk for developing sCJD, mainly in PRNP M129M homozygous subjects with early onset. These results extend the very short list of genes (other than PRNP) involved in the development of human prion diseases; and support the notion that similar to AD, in sCJD several loci may contribute with modest overall effects to disease risk. These findings underscore the interplay in both pathologies of APP, Aβ oligomers, ApoE, PrP and BACE1, and suggest that aging and perhaps vascular risk factors may modulate disease pathologies in part through these key players.es_ES
dc.description.sponsorshipThis work was supported by grants FIS 05/0912 from the Ministerio de Ciencia e Innovación, DGSP from Ministerio de Sanidad, Política Social e Igualdad (MC), the DGSP of the Spanish National Health Ministry (MC), and the Spanish CIBERNED (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas) network (AL, JdPC, IF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptes_ES
dc.publisherPublic Library of Sciencees_ES
dc.relation.isversionofPublisher's versiones_ES
dc.subject.meshAged es_ES
dc.subject.meshAmyloid Precursor Protein Secretases es_ES
dc.subject.meshAspartic Acid Endopeptidases es_ES
dc.subject.meshCase-Control Studies es_ES
dc.subject.meshCodon es_ES
dc.subject.meshCreutzfeldt-Jakob Syndrome es_ES
dc.subject.meshGenetic Predisposition to Disease es_ES
dc.subject.meshHumans es_ES
dc.subject.meshPolymorphism, Single Nucleotidees_ES
dc.titleA common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob diseasees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Ciencia e Innovación (España)es_ES
dc.contributor.funderMinisterio de Sanidad Política Social e Igualdad (España)es_ES
dc.identifier.journalPloS onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiologíaes_ES

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