Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host.
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.
Meyer-Luehmann
Melanie
M
Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
Coomaraswamy
Janaky
J
Bolmont
Tristan
T
Kaeser
Stephan
S
Schaefer
Claudia
C
Kilger
Ellen
E
Neuenschwander
Anton
A
Abramowski
Dorothee
D
Frey
Peter
P
Jaton
Anneliese L
AL
Vigouret
Jean-Marie
JM
Paganetti
Paolo
P
Walsh
Dominic M
DM
Mathews
Paul M
PM
Ghiso
Jorge
J
Staufenbiel
Matthias
M
Walker
Lary C
LC
Jucker
Mathias
M
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
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D014020:Tissue Extracts