Evidence for Seeding of β-Amyloid by Intracerebral Infusion of Alzheimer Brain Extracts in β-Amyloid Precursor Protein-Transgenic Mice
Open accessAbstract
Many neurodegenerative diseases are associated with the abnormal sequestration of disease-specific proteins in the brain, but the events that initiate this process remain unclear. To determine whether the deposition of the β-amyloid peptide (Aβ), a key pathological feature of Alzheimer's disease (AD), can be induced in vivo , we infused dilute supernatants of autopsy-derived neocortical homogenates from Alzheimer's patients unilaterally into the hippocampus and neocortex of 3-month-old β-amyloid precursor protein (βAPP)-transgenic mice. Up to 4 weeks after the infusion there was no Aβ-deposition in the brain; however, after 5 months, the AD-tissue-injected hemisphere of the transgenic mice had developed profuse Aβ-immunoreactive senile plaques and vascular deposits, some of which were birefringent with Congo Red. There was limited deposition of diffuse Aβ also in the brains of βAPP-transgenic mice infused with tissue from an age-matched, non-AD brain with mild β-amyloidosis, but none in mice receiving extract from a young control case. Aβ deposits also were not found in either vehicle-injected or uninjected transgenic mice or in any nontransgenic mice. The results show that cerebral β-amyloid can be seeded in vivo by a single inoculation of dilute AD brain extract, demonstrating a key pathogenic commonality between β-amyloidosis and other neurodegenerative diseases involving abnormal protein polymerization. The paradigm can be used to clarify the conditions that initiate in vivo β-amyloidogenesis in the brain and may yield a more authentic animal model of Alzheimer's disease and other neurodegenerative disorders.
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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 [49]
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- Authors
- Kane, M. D., Lipinski, W. J., Callahan, M. J., Bian, F., Durham, R. A., Schwarz, R. D., Roher, A. E., & Walker, L. C.
- Affiliations
- Banner Sun Health Research Institute (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-05-15
- Volume
- 20
- Issue
- 10
- Pages
- 3606-3611
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6772682
- OpenAlex
- W2171495114
- Cited by
- 394
- References
- 33
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 13 · 2023: 10 · 2022: 27 · 2021: 22 · 2020: 31 · 2019: 20 · 2018: 18 · 2017: 19 · 2016: 27 · 2015: 34 · 2014: 31 · 2013: 37 · 2012: 16
- FWCI
- 3.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, intracerebral infusion, amyloid plaques, vascular amyloid deposits, Congo red birefringence, amyloidosis, neurodegeneration pathogenesis, protein polymerization, animal models of Alzheimer's disease
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Animals, Antigen-Antibody Reactions, Cerebral Arteries, Congo Red, Disease Models, Animal, Coloring Agents, Encephalitis, Female, Hippocampus, Humans, Injections, Intraventricular, Male, Mice, Transgenic, Nerve Degeneration, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Mice
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