Ablation of prion protein in wild type human amyloid precursor protein (APP) transgenic mice does not alter the proteolysis of APP, levels of amyloid-β or pathologic phenotype

Isobel Whitehouse, Deborah Brown, Herbert Baybutt, Abigail Diack, Pedro Piccardo, Jean Manson, Nigel M Hooper

Research output: Contribution to journalArticlepeer-review

Abstract

The cellular prion protein (PrPC) has been proposed to play an important role in the pathogenesis of Alzheimer's disease. In cellular models PrPC inhibited the action of the β-secretase BACE1 on wild type amyloid precursor protein resulting in a reduction in amyloid-β (Aβ) peptides. Here we have assessed the effect of genetic ablation of PrPC in transgenic mice expressing human wild type amyloid precursor protein (line I5). Deletion of PrPC had no effect on the α- and β-secretase proteolysis of the amyloid precursor protein (APP) nor on the amount of Aβ38, Aβ40 or Aβ42 in the brains of the mice. In addition, ablation of PrPC did not alter Aβ deposition or histopathology phenotype in this transgenic model. Thus using this transgenic model we could not provide evidence to support the hypothesis that PrPC regulates Aβ production.
Original languageEnglish
Article numbere0159119
JournalPLoS ONE
Volume11
Issue number7
Early online date22 Jul 2016
DOIs
Publication statusE-pub ahead of print - 22 Jul 2016

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