Cellular prion protein and Alzheimer disease Link to oligomeric amyloid-β and neuronal cell death

Soluble oligomeric amyloid-beta (A beta) has been suggested to impair synaptic and neuronal function, leading to neurodegeneration that is clinically observed as the memory and cognitive dysfunction characteristic of Alzheimer disease, while the precise mechanism(s) whereby oligomeric A beta causes neurotoxicity remains unknown. Recently, the cellular prion protein (PrPC) was reported to be an essential co-factor in mediating the neurotoxic effect of oligomeric A beta. Our recent study showed that Prnp(-/-) mice are resistant to the neurotoxic effect of oligomeric A beta in vivo and in vitro. Furthermore, application of an anti-PrPC antibody or PrPC peptide was able to block oligomeric A beta-induced neurotoxicity. These findings demonstrate that PrPC may be involved in neuropathologic conditions other than conventional prion diseases, i.e., Creutzfeldt-Jakob disease.