Ablation of Prion Protein in Wild Type Human Amyloid Precursor Protein (APP) Transgenic Mice Does Not Alter The Proteolysis of APP, Levels of Amyloid-[beta] or Pathologic Phenotype

The cellular prion protein (PrP.sup.C) has been proposed to play an important role in the pathogenesis of Alzheimer's disease. In cellular models PrP.sup.C inhibited the action of the [beta]-secretase BACE1 on wild type amyloid precursor protein resulting in a reduction in amyloid-[beta] (A[bet...

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Bibliographic Details
Published in:PloS one 2016-07, Vol.11 (7), p.e0159119
Main Authors: Whitehouse, Isobel J, Brown, Deborah, Baybutt, Herbert, Diack, Abigail B, Kellett, Katherine A. B, Piccardo, Pedro, Manson, Jean C, Hooper, Nigel M
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amyloid beta-protein
Analysis
Care and treatment
Diagnosis
Gene mutation
Genetic aspects
Genetically modified mice
Proteolysis
Risk factors
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Summary:The cellular prion protein (PrP.sup.C) has been proposed to play an important role in the pathogenesis of Alzheimer's disease. In cellular models PrP.sup.C inhibited the action of the [beta]-secretase BACE1 on wild type amyloid precursor protein resulting in a reduction in amyloid-[beta] (A[beta]) peptides. Here we have assessed the effect of genetic ablation of PrP.sup.C in transgenic mice expressing human wild type amyloid precursor protein (line I5). Deletion of PrP.sup.C had no effect on the [alpha]- and [beta]-secretase proteolysis of the amyloid precursor protein (APP) nor on the amount of A[beta]38, A[beta]40 or A[beta]42 in the brains of the mice. In addition, ablation of PrP.sup.C did not alter A[beta] deposition or histopathology phenotype in this transgenic model. Thus using this transgenic model we could not provide evidence to support the hypothesis that PrP.sup.C regulates A[beta] production.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0159119