Cellular prion protein mediates the toxicity of beta-amyloid oligomers: implications for Alzheimer disease.
Alzheimer disease (AD) is the most common cause of age-related dementia, affecting more than 25 million people worldwide. The accumulation of insoluble beta-amyloid (Abeta) plaques in the brain has long been considered central to the pathogenesis of AD. However, recent evidence suggests that soluble oligomeric assemblies of Abeta may be of greater importance. beta-Amyloid oligomers have been found to be potent synaptotoxins, but the mechanism by which they exert their action has remained elusive. Herein, we review the recently published finding that cellular prion protein (PrP(c)) is a high-affinity receptor for Abeta oligomers, mediating their toxic effects on synaptic plasticity. We further discuss the relationship between AD and PrP(c) and the potential clinical implications. Cellular prion protein may provide a novel target for therapeutic intervention in AD.
Nygaard
Haakon B
HB
Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06536-0812, USA.
Strittmatter
Stephen M
SM
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D006801:Humans; D010446:Peptide Fragments / Q000378:metabolism; D018621:PrPC Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D018621:PrPC Proteins