Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host
Open accessAbstract
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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Cerebral β-amyloidosis can be exogenously induced by exposure to dilute brain extracts containing aggregated Aβ seeds.
“Experimentally, cerebral β-amyloidosis can be exogenously induced by exposure to dilute brain extracts containing aggregated Aβ seeds.”
From Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders (2011) · cites this paper as [51]
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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
- ORCID
- 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
- green
- infoscience.epfl.ch
- 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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