title: Cellular prion protein participates in amyloid-β transcytosis across the blood-brain barrier.
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.
authors.affiliation: Molecular Neurodegeneration, Institute of Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Pflanzner
authors.forename: Benjamin
authors.initials: B
authors.lastname: Petsch
authors.forename: Bettina
authors.initials: B
authors.lastname: André-Dohmen
authors.forename: Andreas
authors.initials: A
authors.lastname: Müller-Schiffmann
authors.forename: Sabrina
authors.initials: S
authors.lastname: Tschickardt
authors.forename: Sascha
authors.initials: S
authors.lastname: Weggen
authors.forename: Lothar
authors.initials: L
authors.lastname: Stitz
authors.forename: Carsten
authors.initials: C
authors.lastname: Korth
authors.forename: Claus U
authors.initials: CU
authors.lastname: Pietrzik
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D051379:Mice; D008954:Models, Biological; D010446:Peptide Fragments / Q000378:metabolism*; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000235:genetics; D057900:Transcytosis
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D018621:PrPC Proteins; C078592:amyloid beta-protein (1-40)