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 language | English |
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Article number | e59554 |
Journal | PLoS ONE |
Volume | 8 |
Issue number | 4 |
DOIs | |
Publication status | Published - 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