| First Author | Baglietto-Vargas D | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 2421 |
| PubMed ID | 33893290 | Mgi Jnum | J:304519 |
| Mgi Id | MGI:6695262 | Doi | 10.1038/s41467-021-22624-z |
| Citation | Baglietto-Vargas D, et al. (2021) Generation of a humanized Abeta expressing mouse demonstrating aspects of Alzheimer's disease-like pathology. Nat Commun 12(1):2421 |
| abstractText | The majority of Alzheimer's disease (AD) cases are late-onset and occur sporadically, however most mouse models of the disease harbor pathogenic mutations, rendering them better representations of familial autosomal-dominant forms of the disease. Here, we generated knock-in mice that express wildtype human Abeta under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Abeta sequence to its wild-type human counterpart leads to age-dependent impairments in cognition and synaptic plasticity, brain volumetric changes, inflammatory alterations, the appearance of Periodic Acid-Schiff (PAS) granules and changes in gene expression. In addition, when exon 14 encoding the Abeta sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAbeta expression, rescues cognition and reduces the formation of PAS granules. |
