Amyloid-beta oligomers increase the localization of prion protein at the cell surface.

In Alzheimer’s disease, the amyloid-b peptide (Ab) 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 Ab. We show here that Ab oligomers signal in cells in a PrPC-dependent manner, as might be expected if Ab oligomers use PrPC as a receptor. Immunofluorescence, flow cytometry and cell surface protein biotinylation experiments indicated that treatment with Ab 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 Ab oligomers, we used live cell confocal and total internal reflection microscopy in cell lines. Ab oligomers inhibited the constitutive endocytosis of PrP^C, but we also found that after Ab oligomer- treatment PrP^C formed more clusters at the cell surface, suggesting the possibility of multiple effects of Ab oligomers. Our experiments show for the first time that Ab oligomers signal in a PrP^C-dependent way and that they can affect PrPC trafficking, increasing its localization at the cell surface. [ABSTRACT FROM AUTHOR]