title: Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host.
abstract: Protein aggregation is an established pathogenic mechanism in Alzheimer's disease, but little is known about the initiation of this process in vivo. Intracerebral injection of dilute, amyloid-beta (Abeta)-containing brain extracts from humans with Alzheimer's disease or beta-amyloid precursor protein (APP) transgenic mice induced cerebral beta-amyloidosis and associated pathology in APP transgenic mice in a time- and concentration-dependent manner. The seeding activity of brain extracts was reduced or abolished by Abeta immunodepletion, protein denaturation, or by Abeta immunization of the host. The phenotype of the exogenously induced amyloidosis depended on both the host and the source of the agent, suggesting the existence of polymorphic Abeta strains with varying biological activities reminiscent of prion strains.
authors.affiliation: Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Meyer-Luehmann
authors.forename: Janaky
authors.initials: J
authors.lastname: Coomaraswamy
authors.forename: Tristan
authors.initials: T
authors.lastname: Bolmont
authors.forename: Stephan
authors.initials: S
authors.lastname: Kaeser
authors.forename: Claudia
authors.initials: C
authors.lastname: Schaefer
authors.forename: Ellen
authors.initials: E
authors.lastname: Kilger
authors.forename: Anton
authors.initials: A
authors.lastname: Neuenschwander
authors.forename: Dorothee
authors.initials: D
authors.lastname: Abramowski
authors.forename: Peter
authors.initials: P
authors.lastname: Frey
authors.forename: Anneliese L
authors.initials: AL
authors.lastname: Jaton
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Vigouret
authors.forename: Paolo
authors.initials: P
authors.lastname: Paganetti
authors.forename: Dominic M
authors.initials: DM
authors.lastname: Walsh
authors.forename: Paul M
authors.initials: PM
authors.lastname: Mathews
authors.forename: Jorge
authors.initials: J
authors.lastname: Ghiso
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.forename: Lary C
authors.initials: LC
authors.lastname: Walker
authors.forename: Mathias
authors.initials: M
authors.lastname: Jucker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000008:administration & dosage* / Q000494:pharmacology; D000686:Amyloidosis / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D001927:Brain Diseases / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006624:Hippocampus / Q000737:chemistry* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011489:Protein Denaturation; D013997:Time Factors; D014020:Tissue Extracts
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D014020:Tissue Extracts