Cellular prion protein participates in amyloid-β transcytosis across the blood-brain barrier

The blood-brain barrier (BBB) facilitates amyloid-beta (A beta) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrPc), a putative receptor implicated in mediating A beta neurotoxicity in Alzheimer's disease (AD), participates in A beta transcytosis across the BBB. Using an in vitro BBB model, [I-125]-A beta(1-40) transcytosis was reduced by genetic knockout of PrPc or after addition of a competing PrPc-specific antibody. Furthermore, we provide evidence that PrPc is expressed in endothelial cells and, that monomeric A beta(1-40) binds to PrPc. These observations provide new mechanistic insights into the role of PrPc in AD. Journal of Cerebral Blood Flow & Metabolism (2012) 32, 628-632; doi:10.1038/jcbfm.2012.7; published online 1 February 2012