Marked increase of neuronal prion protein immunoreactivity in Alzheimer's disease and human prion diseases

Abstract.

In neurodegenerative disorders including Alzheimer's disease (AD), free radical damage to lipids, carbohydrates, proteins and DNA has been demonstrated to play a key pathogenetic role. In vitro studies have suggested a function of the cellular prion protein (PrP^c) in the defense against oxidative stress. Therefore, we investigated the distribution of PrP^c immunoreactivity in hippocampus (sectors CA4–CA1), subiculum (Sub), entorhinal (EC), and temporal cortex (TC) in sections from AD, human transmissible spongiform encephalopathy (TSE) and control brains. Compared to control cases, AD brains revealed an increase in the proportion of PrP^c-immunoreactive neurons, which was statistically significant in CA2, Sub, and TC. In TSEs, a statistically significant increase of PrP^c-immunoreactive neurons was observed in CA2, CA1, Sub, EC, and TC. In conclusion, our data show a striking up-regulation of PrP^c in neurodegeneration and provide additional support for the concept that PrP^c may be involved in the defense against oxidative stress.