Dataset Information

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

ABSTRACT: The cellular prion protein (PrP(C)) has been implicated in the development of Alzheimer's disease (AD). PrP(C) decreases amyloid-? (A?) production, which is involved in AD pathogenesis, by inhibiting ?-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), A? load (rs?=?-0.456, p?=?0.001), soluble A? (rs?=?-0.283, p?=?0.026) and insoluble A? (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 A? load (rs?=?0.040, p?=?0.393), soluble A? (rs?=?0.113, p?=?0.223) or insoluble A? (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 A? production and indicate that brain PrP(C) level may be important in influencing the onset and progression of sporadic AD.

SUBMITTER: Whitehouse IJ

PROVIDER: S-EPMC3618446 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Whitehouse Isobel J IJ Miners J Scott JS Glennon Elizabeth B C EB Kehoe Patrick G PG Love Seth S Kellett Katherine A B KA Hooper Nigel M NM

PloS one 20130405 4

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 wi ...[more]

PMID: 23577068

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Dataset Information

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

Publications

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

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