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PLoS One. 2013;8(4):e59554. doi: 10.1371/journal.pone.0059554. Epub 2013 Apr 5.

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

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1
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.

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.

PMID:
23577068
PMCID:
PMC3618446
DOI:
10.1371/journal.pone.0059554
[Indexed for MEDLINE]
Free PMC Article
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