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

• Published in: PloS one Vol. 8; no. 4; p. e59554
• Main Authors: Whitehouse, Isobel J, Miners, J Scott, Glennon, Elizabeth B C, Kehoe, Patrick G, Love, Seth, Kellett, Katherine A B, Hooper, Nigel M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05-04-2013; Public Library of Science (PLoS)
• Subjects: Advertising executives; Aged; Aged, 80 and over; Alzheimer Disease - enzymology; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Amyloid Precursor Protein Secretases - metabolism; Aspartic Acid Endopeptidases - metabolism; Biology; Brain; Brain - enzymology; Brain - metabolism; Brain - pathology; Brain research; Case-Control Studies; Cellular biology; Comparative analysis; Contactin; Contactins - metabolism; Correlation; Cortex (frontal); Dementia; Development and progression; Down Syndrome - metabolism; Down's syndrome; Enzymes; Female; Frontal Lobe - metabolism; Genome-wide association studies; Genomes; Genomics; Humans; Hypotheses; Male; Medicine; Middle Aged; Neurodegenerative diseases; Neurosciences; Pathogenesis; Pathology; Prion protein; Prions; Prions - metabolism; Protein expression; Proteins; Rodents; Secretase; β-Site APP-cleaving enzyme 1
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059554

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.