A Common BACE1 Polymorphism Is a Risk Factor for Sporadic Creutzfeldt-Jakob Disease
Calero, Olga (Instituto de Salud Carlos III)
Bullido, María J. (Hospital Universitario La Paz (Madrid))
Clarimón, Jordi (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Frank-García, Ana (Hospital Universitario La Paz (Madrid))
Martinez-Martin, Pablo (Instituto de Salud Carlos III)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Rey, María Jesús (Hospital Clínic i Provincial de Barcelona)
Sastre, Isabel (Hospital Universitario La Paz (Madrid))
Rábano, Alberto (Instituto de Salud Carlos III)
de Pedro-Cuesta, Jesús (Instituto de Salud Carlos III)
Ferrer, Isidro (Institut d'Investigació Biomèdica de Bellvitge)
Calero, Miguel (Instituto de Salud Carlos III)
Universitat Autònoma de Barcelona

Data:	2012
Resum:	The 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. © 2012 Calero et al.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 7 Núm. 8 (30 2012) , p. e43926, ISSN 1932-6203

DOI: 10.1371/journal.pone.0043926
PMID: 22952813

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