| First Author | Stöhr J | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 28 | Pages | 10329-34 |
| PubMed ID | 24982137 | Mgi Jnum | J:212279 |
| Mgi Id | MGI:5578423 | Doi | 10.1073/pnas.1408968111 |
| Citation | Stohr J, et al. (2014) Distinct synthetic Abeta prion strains producing different amyloid deposits in bigenic mice. Proc Natl Acad Sci U S A 111(28):10329-34 |
| abstractText | An increasing number of studies continue to show that the amyloid beta (Abeta) peptide adopts an alternative conformation and acquires transmissibility; hence, it becomes a prion. Here, we report on the attributes of two strains of Abeta prions formed from synthetic Abeta peptides composed of either 40 or 42 residues. Modifying the conditions for Abeta polymerization increased both the protease resistance and prion infectivity compared with an earlier study. Approximately 150 d after intracerebral inoculation, both synthetic Abeta40 and Abeta42 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 Abeta40 prions produced amyloid plaques containing both Abeta40 and Abeta42 in the brains of inoculated bigenic mice, whereas synthetic Abeta42 prions stimulated the formation of smaller, more numerous plaques composed predominantly of Abeta42. Synthetic Abeta40 preparations consisted of long straight fibrils; in contrast, the Abeta42 fibrils were much shorter. Addition of 3.47 mM (0.1%) SDS to the polymerization reaction produced Abeta42 fibrils that were indistinguishable from Abeta40 fibrils produced in the absence or presence of SDS. Moreover, the Abeta amyloid plaques in the brains of bigenic mice inoculated with Abeta42 prions prepared in the presence of SDS were similar to those found in mice that received Abeta40 prions. From these results, we conclude that the composition of Abeta plaques depends on the conformation of the inoculated Abeta polymers, and thus, these inocula represent distinct synthetic Abeta prion strains. |
