Unaltered prion protein expression in Alzheimer disease patients

The suggested role of cellular prion protein (PrPC) in mediating the toxic effects of oligomeric amyloid beta peptide (A beta) in Alzheimer disease (AD) is controversial. To address the hypothesis that variable PrPC expression is involved in AD pathogenesis, we analyzed PrPC expression in the frontal and temporal cortices and hippocampus of individuals with no cognitive impairment (NCI), amnestic mild cognitive impairment (aMCI), mild AD (mAD) and AD. We found that PrPC expression in all brain regions was not significantly altered among the various patient groups. In addition, PrPC levels in all groups did not correlate with expression of methionine (M) or valine (V) at codon 129 of the PrP gene, a polymorphism that has been linked in some studies to increased risk for AD, and which occurs in close proximity to the proposed binding region for the oligomeric A beta peptide. Our results indicate that, if PrPC is involved in mediating the toxic effects of the oligomeric A beta peptide, these effects occur independently of steady state levels of PrP or the codon 129 polymorphism.