Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Isobel J Whitehouse  1 , J Scott Miners, Elizabeth B C Glennon, Patrick G Kehoe, Seth Love, Katherine A B Kellett, Nigel M Hooper
Affiliations

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

Isobel J Whitehouse et al. PLoS One. 2013.

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.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. PrPC, but not CNTN5, is decreased in sporadic AD.
Representative immunoblots of PrPC and actin in temporal cortex samples from sporadic AD patients compared to age-matched controls (A) with densitometric analysis relative to actin levels represented in a grouped scatter plot (B). Representative immunoblots of CNTN5 relative to actin (C) with densitometry analysis (D). Line represents mean, *p<0.05, n = 24 per group.
Figure 2
Figure 2. PrPC inversely correlates with BACE1 activity, Aβ load, soluble and insoluble Aβ and Braak stage.
Relative PrPC protein levels were plotted against BACE1 activity (A), Aβ load (B), soluble Aβ (C), insoluble Aβ (D) and Braak stage (E) for each subject in the cohort (n = 48. Control, filled circles; AD, empty circles). PrPC significantly inversely correlates with BACE1 activity, Aβ load, soluble Aβ, insoluble Aβ and Braak stage as determined by Spearman's rank correlation coefficient (rs).
Figure 3
Figure 3. CNTN5 does not correlate with Aβ load, soluble Aβ or insoluble Aβ.
Relative CNTN5 protein levels were plotted against Aβ load (A), soluble Aβ (B) and insoluble Aβ (C) for each subject in the cohort (n = 48. Control, filled circles; AD, empty circles). CNTN5 levels did not correlate with Aβ load, soluble Aβ or insoluble Aβ levels as determined by Spearman's rank correlation coefficient (rs).
Figure 4
Figure 4. PrPC is not reduced in DS brains.
Representative immunoblots of PrPC and actin in temporal cortex samples from Down's syndrome patients compared to age-matched controls (A). Densitometric analysis of PrPC relative to actin levels is represented in grouped scatter plot (B). Line represents mean, *p<0.05, n = 8 control group and n = 9 DS group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Burns A, Iliffe S (2009) Alzheimer's disease. BMJ 338: b158. - PubMed
    1. Mount C, Downton C (2006) Alzheimer disease: progress or profit? Nat Med 12: 780–784. - PubMed
    1. Iqbal K, Alonso Adel C, Chen S, Chohan MO, El-Akkad E, et al. (2005) Tau pathology in Alzheimer disease and other tauopathies. Biochim Biophys Acta 1739: 198–210. - PubMed
    1. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82: 239–259. - PubMed
    1. Cras P, Smith MA, Richey PL, Siedlak SL, Mulvihill P, et al. (1995) Extracellular neurofibrillary tangles reflect neuronal loss and provide further evidence of extensive protein cross-linking in Alzheimer disease. Acta Neuropathol 89: 291–295. - PubMed

Publication types

MeSH terms