Cited by 971Alzheimer's disease research and treatmentsPrion Diseases and Protein MisfoldingDementia and Cognitive Impairment Research

Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host

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Meyer-Luehmann, Melanie, Coomaraswamy, Janaky, Bolmont, Tristan, Kaeser, Stephan, Schaefer, Claudia, Kilger, Ellen, Neuenschwander, Anton, Abramowski, Dorothee +10 more·2006·Science

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-β (Aβ)–containing brain extracts from humans with Alzheimer's disease or β-amyloid precursor protein (APP) transgenic mice induced cerebral β-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 Aβ immunodepletion, protein denaturation, or by Aβ 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 Aβ strains with varying biological activities reminiscent of prion strains.

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Crossref · 10.1126/science.1131864

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Authors
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.
Affiliations
  • Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, D-72076 Tübingen, Germany.
  • University College Dublin (IE)
Corresponding author
  • Coomaraswamy, Janaky
  • Bolmont, Tristan
  • Walker, Lary C.
  • Jucker, Mathias
Venue
Science
Published
2006-09-22
Volume
313
Issue
5794
Pages
1781-1784
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2098022922
Cited by
971
References
31
Citations by year
2026: 22 · 2025: 18 · 2024: 34 · 2023: 31 · 2022: 52 · 2021: 50 · 2020: 47 · 2019: 59 · 2018: 67 · 2017: 57 · 2016: 63 · 2015: 64 · 2014: 73 · 2013: 71 · 2012: 65
FWCI
21.65
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
  • Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders
  • Wellcome Trust
  • National Institute of Neurological Disorders and Stroke (R21NS045357, NS45357)
  • National Center for Research Resources (RR-00 165, P51RR000165)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
amyloid-beta, Alzheimer's disease, brain extracts, protein aggregation, immunodepletion, immunization, host-pathogen interaction
MeSH terms
Aged, Aged, 80 and over, Aging, Alzheimer Disease, Amyloidosis, Animals, Brain, Brain Chemistry, Brain Diseases, Female, Hippocampus, Humans, Male, Mice, Transgenic, Protein Denaturation, Time Factors, Tissue Extracts, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice

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