The prion protein as a receptor for amyloid-β

Abstract

Arising from: J. Laurén et al. Nature 457, 1128–1132 (2009)10.1038/nature07761; Laurén et al. reply Increased levels of brain amyloid-β, a secreted peptide cleavage product of amyloid precursor protein (APP), is believed to be critical in the aetiology of Alzheimer’s disease¹. Increased amyloid-β can cause synaptic depression^2,3, reduce the number of spine protrusions (that is, sites of synaptic contacts)^4,5 and block long-term synaptic potentiation (LTP)^6,7, a form of synaptic plasticity; however, the receptor through which amyloid-β produces these synaptic perturbations has remained elusive. Laurén et al.⁸ suggested that binding between oligomeric amyloid-β (a form of amyloid-β thought to be most active^5,6,9,10,11) and the cellular prion protein (PrP^C)⁸ is necessary for synaptic perturbations. Here we show that PrP^C is not required for amyloid-β-induced synaptic depression, reduction in spine density, or blockade of LTP; our results indicate that amyloid-β-mediated synaptic defects do not require PrP^c.