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

In neurodegenerative disorders including Alzheimer's disease (AD), free rad ical damage to lipids, carbohydrates, proteins and DNA has been demonstrate d to play a key pathogenetic role. In vitro studies have suggested a functi on of the cellular prion protein (PrPc) in the defense against oxidative st ress. Therefore, we investigated the distribution of PrPc immunoreactivity in hippocampus (sectors CA4-CA1), subiculum (Sub), entorhinal (EC), and tem poral cortex (TC) in sections from AD, human transmissible spongiform encep halopathy (TSE) and control brains. Compared to control cases, AD brains re vealed an increase in the proportion of PrPc-immunoreactive neurons, which was statistically significant in CA2, Sub, and TC. In TSEs, a statistically significant increase of PrPc-immunoreactive neurons was observed in CA2, C AI, Sub, EC, and TC. In conclusion, our data show a striking up-regulation of PrPc in neurodegeneration and provide additional support for the concept that PrPc may be involved in the defense against oxidative stress.