Caetano_2011_J.Neurochem_117_538

In Alzheimer's disease, the amyloid-beta peptide (Abeta) interacts with distinct proteins at the cell surface to interfere with synaptic communication. Recent data have implicated the prion protein (PrP(C)) as a putative receptor for Abeta. We show here that Abeta oligomers signal in cells in a PrP(C)-dependent manner, as might be expected if Abeta oligomers use PrP(C) as a receptor. Immunofluorescence, flow cytometry and cell surface protein biotinylation experiments indicated that treatment with Abeta oligomers, but not monomers, increased the localization of PrP(C) at the cell surface in cell lines. These results were reproduced in hippocampal neuronal cultures by labeling cell surface PrP(C). In order to understand possible mechanisms involved with this effect of Abeta oligomers, we used live cell confocal and total internal reflection microscopy in cell lines. Abeta oligomers inhibited the constitutive endocytosis of PrP(C), but we also found that after Abeta oligomer-treatment PrP(C) formed more clusters at the cell surface, suggesting the possibility of multiple effects of Abeta oligomers. Our experiments show for the first time that Abeta oligomers signal in a PrP(C)-dependent way and that they can affect PrP(C) trafficking, increasing its localization at the cell surface.