NR AVGF
AU Meyer-Luehmann,M.; Coomaraswamy,J.; Bolmont,T.; Kaeser,S.; Schaefer,C.; Kilger,E.; Neuenschwander,A.; Abramowski,D.; Frey,P.; Jaton,A.L.; Vigouret,J.M.; Paganetti,P.; Walsh,D.M.; Mathews,P.M.; Ghiso,J.; Staufenbiel,M.; Walker,L.C.; Jucker,M.
TI Exogenous induction of cerebral beta-amyloidogenesis is governed by agent and host
QU Science 2006 Sep 22; 313(5794): 1781-4
PT journal article
AB 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.
MH Aged; Aged, 80 and over; Aging; Alzheimer Disease/metabolism; Amyloid beta-Protein/*administration &; dosage/*analysis/chemistry/pharmacology; Amyloid beta-Protein Precursor/*administration & dosage/pharmacology; Amyloidosis/*metabolism/pathology; Animals; Brain/pathology; Brain Chemistry; Brain Diseases/*metabolism/pathology; Female; Hippocampus/*chemistry/pathology; Humans; Male; Mice; Mice, Transgenic; Protein Denaturation; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Time Factors; Tissue Extracts
AD Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
SP englisch
PO USA