| First Author | Xia D | Year | 2016 |
| Journal | Neuron | Volume | 90 |
| Issue | 2 | Pages | 417-22 |
| PubMed ID | 27100200 | Mgi Jnum | J:239477 |
| Mgi Id | MGI:5828967 | Doi | 10.1016/j.neuron.2016.03.009 |
| Citation | Xia D, et al. (2016) Loss of Abeta43 Production Caused by Presenilin-1 Mutations in the Knockin Mouse Brain. Neuron 90(2):417-22 |
| abstractText | We recently reported that homozygous Presenilin-1 (Psen1) knockin (KI) mice carrying the familial Alzheimer's disease (FAD) mutation L435F or C410Y recapitulate the phenotypes of Psen1(-/-) mice. Production and steady-state levels of Abeta40 and Abeta42 are undetectable in KI/KI brains and reduced in KI/+ brains, though the Abeta42/Abeta40 ratio is slightly increased in KI/+ brains. Moreover, the FAD mutation impairs synaptic function, learning and memory, and age-dependent neuronal survival in the adult brain. Here we extend our analysis of the effects of the L435F and C410Y mutations to the generation of Abeta43. Similar to Abeta40 and Abeta42, production of Abeta43 is undetectable in KI/KI brains and reduced in KI/+ brains. These results support our previous conclusions that the L435F and C410Y mutations cause loss of Presenilin function and gamma-secretase activity, including impaired Abeta production in the brain. This Matters Arising Response paper addresses the Veugelen et al. (2016) Matters Arising paper, published concurrently in Neuron. |
