A common BACE1 polymorphism Is a risk factor for sporadic Creutzfeldt-Jakob disease
Entity
UAM. Departamento de MedicinaPublisher
Public Library of ScienceDate
2012-08-30Citation
10.1371/journal.pone.0043926
Plos One 7.8 (2012): e43926
ISSN
1932-6203 (online)DOI
10.1371/journal.pone.0043926Funded by
This 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)Subjects
Amyloid precursor protein secretases; Creutzfeldt-Jakob Syndrome; Case-Control Studies; Aspartic Acid Endopeptidases; Polymorphism; MedicinaRights
© 2012 Calero et alAbstract
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
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Google Scholar:Calero, Olga
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Bullido Gómez-Heras, María Jesús
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Clarimon, Jordi
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Frank García, Ana
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Martínez-Martín, Pablo
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Lleõ, Alberto
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Rey, María Jesús
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Sastre, Isabel
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Rábano, Alberto
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De Pedro-Cuesta, Jesús
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Ferrer, Isidre
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Calero, Miguel
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