Soluble Aβ Seeds Are Potent Inducers of Cerebral β-Amyloid Deposition
Open Access
- 12 October 2011
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (41), 14488-14495
- https://doi.org/10.1523/jneurosci.3088-11.2011
Abstract
Cerebral β-amyloidosis and associated pathologies can be exogenously induced by the intracerebral injection of small amounts of pathogenic Aβ-containing brain extract into young β-amyloid precursor protein (APP) transgenic mice. The probable β-amyloid-inducing factor in the brain extract has been identified as a species of aggregated Aβ that is generated in its most effective conformation or compositionin vivo. Here we report that Aβ in the brain extract is more proteinase K (PK) resistant than is synthetic fibrillar Aβ, and that this PK-resistant fraction of the brain extract retains the capacity to induce β-amyloid deposition upon intracerebral injection in young, pre-depositing APP23 transgenic mice. After ultracentrifugation of the brain extract, in vivo. The finding that small and soluble Aβ seeds are potent inducers of cerebral β-amyloidosis raises the possibility that such seeds may mediate the spread of β-amyloidosis in the brain. If they can be identifiedin vivo, soluble Aβ seeds in bodily fluids also could serve as early biomarkers for cerebral β-amyloidogenesis and eventually Alzheimer's disease.Keywords
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