| First Author | Hornung K | Year | 2019 |
| Journal | J Alzheimers Dis | Volume | 67 |
| Issue | 3 | Pages | 849-858 |
| PubMed ID | 30664509 | Mgi Jnum | J:286211 |
| Mgi Id | MGI:6402356 | Doi | 10.3233/JAD-181134 |
| Citation | Hornung K, et al. (2019) N-Terminal Truncated Abeta4-42 Is a Substrate for Neprilysin Degradation in vitro and in vivo. J Alzheimers Dis 67(3):849-858 |
| abstractText | In sporadic Alzheimer's disease (AD), an imbalance between production and clearance of amyloid-beta (Abeta) peptides seems to account for enhanced Abeta accumulation. The metalloprotease neprilysin (NEP) is an important Abeta degrading enzyme as shown by a variety of in vitro and in vivo studies. While the degradation of full-length Abeta peptides such as Abeta1-40 and Abeta1-42 is well established, it is less clear whether NEP is also capable of degrading N-terminally truncated Abeta species such as the common variant Abeta4-42. In the present report, we confirmed the degradation of Abeta4-x species by neprilysin using in vitro digestion and subsequent analysis using gel-based assays and mass spectrometry. By crossing Tg4-42 mice expressing only Abeta4-42 peptides with homozygous NEP-knock-out mice (NEP-/-), we were able to demonstrate that NEP deficiency increased hippocampal intraneuronal Abeta levels and aggravated neuron loss in the Tg4-42 transgenic mouse model of AD. |
