Distinct synthetic A? prion strains producing different amyloid deposits in bigenic mice.

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

SUBMITTER: Stohr J 

PROVIDER: S-EPMC4104853 | biostudies-other | 2014 Jul

REPOSITORIES: biostudies-other