Distinct synthetic Aβ prion strains producing different amyloid deposits in bigenic mice

An increasing number of studies continue to show that the amyloid beta (A beta) peptide adopts an alternative conformation and acquires transmissibility; hence, it becomes a prion. Here, we report on the attributes of two strains of A beta prions formed from synthetic A beta peptides composed of either 40 or 42 residues. Modifying the conditions for A beta polymerization increased both the protease resistance and prion infectivity compared with an earlier study. Approximately 150 d after intracerebral inoculation, both synthetic A beta 40 and A beta 42 prions produced a sustained rise in the bioluminescence imaging signal in the brains of bigenic Tg(APP23: Gfap-luc) mice, indicative of astrocytic gliosis. Pathological investigations showed that synthetic A beta 40 prions produced amyloid plaques containing both A beta 40 and A beta 42 in the brains of inoculated bigenic mice, whereas synthetic A beta 42 prions stimulated the formation of smaller, more numerous plaques composed predominantly of A beta 42. Synthetic A beta 40 preparations consisted of long straight fibrils; in contrast, the A beta 42 fibrils were much shorter. Addition of 3.47 mM (0.1%) SDS to the polymerization reaction produced A beta 42 fibrils that were indistinguishable from A beta 40 fibrils produced in the absence or presence of SDS. Moreover, the A beta amyloid plaques in the brains of bigenic mice inoculated with A beta 42 prions prepared in the presence of SDS were similar to those found in mice that received A beta 40 prions. From these results, we conclude that the composition of A beta plaques depends on the conformation of the inoculated A beta polymers, and thus, these inocula represent distinct synthetic A beta prion strains.