2026-08-12T20:56:29Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/68392025-03-27T08:20:50Zcom_20.500.12105_2052com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19608col_20.500.12105_19609col_20.500.12105_16962col_20.500.12105_16963
Repisalud
author
Calero, Olga
author
Bullido, María Jesús
author
Clarimón, Jordi
author
Frank-García, Ana
author
Martinez-Martin, Pablo
author
Lleó, Alberto
author
Rey, María Jesús
author
Sastre, Isabel
author
Rábano, Alberto
author
Pedro-Cuesta, Jesus de
author
Ferrer, Isidro
author
Calero, Miguel
funder
Ministerio de Ciencia e Innovación (España)
funder
Ministerio de Sanidad Política Social e Igualdad (España)
2018-12-13T10:56:21Z
2018-12-13T10:56:21Z
2012-08-30
PLoS One. 2012;7(8):e43926.
10.1371/journal.pone.0043926
1932-6203
1932-6203
PloS one
22952813
http://hdl.handle.net/20.500.12105/6839
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.
eng
A common BACE1 polymorphism is a risk factor for sporadic Creutzfeldt-Jakob disease
research article
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URL
https://repisalud.isciii.es/bitstreams/f5f31827-e09d-4838-b64a-33eae8725088/download
File
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application/pdf
ACommonBACE1Polymorphism_2012.pdf
URL
https://repisalud.isciii.es/bitstreams/97528082-3dd9-487f-8dff-305b96317277/download
File
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ACommonBACE1Polymorphism_2012.pdf.txt