| First Author | Qin K | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 8524 |
| PubMed ID | 31189938 | Mgi Jnum | J:281589 |
| Mgi Id | MGI:6357339 | Doi | 10.1038/s41598-019-44317-w |
| Citation | Qin K, et al. (2019) "Dual Disease" TgAD/GSS mice exhibit enhanced Alzheimer's disease pathology and reveal PrP(C)-dependent secretion of Abeta. Sci Rep 9(1):8524 |
| abstractText | To address the question of cross-talk between prion protein (PrP) and Alzheimer's disease (AD), we generated TgAD/GSS mice that develop amyloid-beta (Abeta) plaques of AD and PrP (specifically mutated PrP(A116V)) plaques of Gerstmann-Straussler-Scheinker disease (GSS) and compared plaque-related features in these mice to AD mice that express normal (TgAD), high (TgAD/HuPrP), or no (TgAD/PrP(-/-)) PrP(C). In contrast to PrP(C), PrP(A116V) weakly co-localized to Abeta plaques, did not co-immunoprecipitate with Abeta, and poorly bound to Abeta in an ELISA-based binding assay. Despite the reduced association of PrP(A116V) with Abeta, TgAD/GSS and TgAD/HuPrP mice that express comparable levels of PrP(A116V) and PrP(C) respectively, displayed similar increases in Abeta plaque burden and steady state levels of Abeta and its precursor APP compared with TgAD mice. Our Tg mouse lines also revealed a predominance of intracellular Abeta plaques in mice lacking PrP(C) (TgAD/PrP(-/-), TgAD/GSS) compared with an extracellular predominance in PrP(C)-expressing mice (TgAD, TgAD/HuPrP). Parallel studies in N2aAPPswe cells revealed a direct dependence on PrP(C) but not PrP(A116V) for exosome-related secretion of Abeta. Overall, our findings are two-fold; they suggest that PrP expression augments Abeta plaque production, at least in part by an indirect mechanism, perhaps by increasing steady state levels of APP, while they also provide support for a fundamental role of PrP(C) to bind to and deliver intraneuronal Abeta to exosomes for secretion. |
