The neurodegeneration in Alzheimer disease and the prion protein

The concept of prion-like has been proposed to explain the pathogenic mechanism of the principal neurodegenerative disorders associated with protein misfolding, including Alzheimer disease (AD). Other evidence relates prion protein with AD: the cellular prion protein (PrPC) binds beta amyloid oligomers, allegedly responsible for the neurodegeneration in AD, mediating their toxic effects. We and others have confirmed the high-affinity binding between beta amyloid oligomers and PrPC, but we were not able to assess the functional consequences of this interaction using behavioral investigations and in vitro tests. This discrepancy rather than being resolved with the classic explanations, differencies in methodological aspects, has been reinforced by new data from different sources. Here we present data obtained with PrP antibody that not interfere with the neurotoxic activity of beta amyloid oligomers. Since the potential role of the PrPC in the neuronal dysfunction induced by beta amyloid oligomers is an important issue, find reasonable explanation of the inconsistent results is needed. Even more important however is the relevance of this interaction in the context of the disease, so as to develop valid therapeutic strategies.