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

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The cellular prion protein (PrPC) has been implicated in the development of Alzheimer's disease (AD). PrPC 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 PrPC 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. PrPC 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). PrPC 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 PrPC 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). PrPC 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 PrPC in the DS brains compared to controls (p = 0.625). These data are consistent with a role for PrPC in regulating Aβ production and indicate that brain PrPC level may be important in influencing the onset and progression of sporadic AD. © 2013 Whitehouse et al.
    Original languageEnglish
    Article numbere59554
    JournalPLoS ONE
    Volume8
    Issue number4
    DOIs
    Publication statusPublished - 5 Apr 2013

    Keywords

    • Aged
    • Aged, 80 and over
    • Alzheimer Disease/enzymology/*metabolism/*pathology
    • Amyloid Precursor Protein Secretases/*metabolism
    • Amyloid beta-Peptides/*metabolism
    • Aspartic Acid Endopeptidases/*metabolism
    • Brain/enzymology/*metabolism/pathology
    • Case-Control Studies
    • Contactins/metabolism
    • Down Syndrome/metabolism
    • Female
    • Frontal Lobe/metabolism
    • Humans
    • Male
    • Middle Aged
    • Prions/*metabolism

    Research Beacons, Institutes and Platforms

    • Dementia@Manchester

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