Another important lipid-raft associated protein which was shown to play an important role in APP processing is the GPIanchored prion protein (PrP; Naslavsky et al., 1997) . It was demonstrated that PrP c regulates APP processing by inhibiting BACE1 activity and that the effect of PrP c on the β-secretase cleavage of APP requires the localization of PrP c to cholesterol-rich lipid rafts and is mediated by the N-terminal polybasic region of PrP C via interaction with glycosaminoglycans (Parkin et al., 2007) . This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves wild type APP but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP Swe ). Although deletion of PrP c in transgenic mice expressing human mutated APP Swe , Ind had no effect on APP processing and Aβ levels, deletion of PrP c in HEK293 cells expression wild type reduced APP cleavage by BACE1. Because there was no effect of PrP c deletion on processing of APP Swe in HEK cells the authors suggested that PrP c may be a key protective player against sporadic Alzheimer disease versus its less common familiar form (Griffiths et al., 2011) . Because there is no detected decrease of PrP c content in the AD brain (Saijo et al., 2011) it is possible to suggest that age-and disease-dependent disruption of lipid rafts might be a cause of decreased ability of PrP c to control BACE1 activity resulting in accumulation of Aβ peptide in the case of sporadic AD.