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Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):11025-30. doi: 10.1073/pnas.1206555109. Epub 2012 Jun 18.

Purified and synthetic Alzheimer's amyloid beta (Aβ) prions.

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  • 1Institute for Neurodegenerative Diseases, University of California, San Francisco, CA 94143, USA.

Abstract

The aggregation and deposition of amyloid-β (Aβ) peptides are believed to be central events in the pathogenesis of Alzheimer's disease (AD). Inoculation of brain homogenates containing Aβ aggregates into susceptible transgenic mice accelerated Aβ deposition, suggesting that Aβ aggregates are capable of self-propagation and hence might be prions. Recently, we demonstrated that Aβ deposition can be monitored in live mice using bioluminescence imaging (BLI). Here, we use BLI to probe the ability of Aβ aggregates to self-propagate following inoculation into bigenic mice. We report compelling evidence that Aβ aggregates are prions by demonstrating widespread cerebral β-amyloidosis induced by inoculation of either purified Aβ aggregates derived from brain or aggregates composed of synthetic Aβ. Although synthetic Aβ aggregates were sufficient to induce Aβ deposition in vivo, they exhibited lower specific biological activity compared with brain-derived Aβ aggregates. Our results create an experimental paradigm that should lead to identification of self-propagating Aβ conformations, which could represent novel targets for interrupting the spread of Aβ deposition in AD patients.

PMID:
22711819
[PubMed - indexed for MEDLINE]
PMCID:
PMC3390876
Free PMC Article
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