| First Author | Moore BD | Year | 2018 |
| Journal | J Exp Med | Volume | 215 |
| Issue | 1 | Pages | 283-301 |
| PubMed ID | 29208777 | Mgi Jnum | J:257699 |
| Mgi Id | MGI:6119089 | Doi | 10.1084/jem.20170600 |
| Citation | Moore BD, et al. (2018) Short Abeta peptides attenuate Abeta42 toxicity in vivo. J Exp Med 215(1):283-301 |
| abstractText | Processing of amyloid-beta (Abeta) precursor protein (APP) by gamma-secretase produces multiple species of Abeta: Abeta40, short Abeta peptides (Abeta37-39), and longer Abeta peptides (Abeta42-43). gamma-Secretase modulators, a class of Alzheimer's disease therapeutics, reduce production of the pathogenic Abeta42 but increase the relative abundance of short Abeta peptides. To evaluate the pathological relevance of these peptides, we expressed Abeta36-40 and Abeta42-43 in Drosophila melanogaster to evaluate inherent toxicity and potential modulatory effects on Abeta42 toxicity. In contrast to Abeta42, the short Abeta peptides were not toxic and, when coexpressed with Abeta42, were protective in a dose-dependent fashion. In parallel, we explored the effects of recombinant adeno-associated virus-mediated expression of Abeta38 and Abeta40 in mice. When expressed in nontransgenic mice at levels sufficient to drive Abeta42 deposition, Abeta38 and Abeta40 did not deposit or cause behavioral alterations. These studies indicate that treatments that lower Abeta42 by raising the levels of short Abeta peptides could attenuate the toxic effects of Abeta42. |
