Prion protein is decreased in Alzheimer's brain and inversely correlates with BACE1 activity, amyloid-β levels and Braak stage

Isobel J. Whitehouse, J. Scott Miners, Elizabeth B. C. Glennon, Patrick G. Kehoe, Seth Love, Katherine A. B. Kellett*, Nigel M. Hooper

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

19 Citations (Scopus)

Abstract

The cellular prion protein (PrP(C)) has been implicated in the development of Alzheimer's disease (AD). PrP(C) decreases amyloid-β (Aβ) production, which is involved in AD pathogenesis, by inhibiting β-secretase (BACE1) activity. Contactin 5 (CNTN5) has also been implicated in the development of AD by a genome-wide association study. Here we measured PrP(C) and CNTN5 in frontal cortex samples from 24 sporadic AD and 24 age-matched control brains and correlated the expression of these proteins with markers of AD. PrP(C) was decreased in sporadic AD compared to controls (by 49%, p = 0.014) but there was no difference in CNTN5 between sporadic AD and controls (p = 0.217). PrP(C) significantly inversely correlated with BACE1 activity (rs = -0.358, p = 0.006), Aβ load (rs = -0.456, p = 0.001), soluble Aβ (rs = -0.283, p = 0.026) and insoluble Aβ (rs = -0.353, p = 0.007) and PrP(C) also significantly inversely correlated with the stage of disease, as indicated by Braak tangle stage (rs = -0.377, p = 0.007). CNTN5 did not correlate with Aβ load (rs = 0.040, p = 0.393), soluble Aβ (rs = 0.113, p = 0.223) or insoluble Aβ (rs = 0.169, p = 0.125). PrP(C) was also measured in frontal cortex samples from 9 Down's syndrome (DS) and 8 age-matched control brains. In contrast to sporadic AD, there was no difference in PrP(C) in the DS brains compared to controls (p = 0.625). These data are consistent with a role for PrP(C) in regulating Aβ production and indicate that brain PrP(C) level may be important in influencing the onset and progression of sporadic AD.
Original languageEnglish
Article number59554
Pages (from-to)e59554
Number of pages8
JournalPLoS ONE
Volume8
Issue number4
DOIs
Publication statusPublished - 5 Apr 2013

Keywords

  • INSULIN-DEGRADING ENZYME
  • A-BETA
  • PRECURSOR PROTEIN
  • SECRETASE ACTIVITY
  • CELLULAR PRION
  • SYNAPTIC ZINC
  • DISEASE
  • ACCUMULATION
  • NEPRILYSIN
  • CONTACTIN

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