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

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