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

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

SUBMITTER: Stohr J 

PROVIDER: S-EPMC3390876 | biostudies-other | 2012 Jul

REPOSITORIES: biostudies-other