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Cellular prion protein participates in amyloid-β transcytosis across the blood-brain barrier
Thorsten Pflanzner1, Benjamin Petsch, Bettina André-Dohmen
1Molecular Neurodegeneration, Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Abstract:
The blood-brain barrier (BBB) facilitates amyloid-β (Aβ) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrP(c)), a putative receptor implicated in mediating Aβ neurotoxicity in Alzheimer's disease (AD), participates in Aβ transcytosis across the BBB. Using an in vitro BBB model, [(125)I]-Aβ(1-40) transcytosis was reduced by genetic knockout of PrP(c) or after addition of a competing PrP(c)-specific antibody. Furthermore, we provide evidence that PrP(c) is expressed in endothelial cells and, that monomeric Aβ(1-40) binds to PrP(c). These observations provide new mechanistic insights into the role of PrP(c) in AD.
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