2026-05-28T19:45:33Zhttps://riuma.uma.es/rest/oai/request

oai:riuma.uma.es:10630/337842026-03-13T07:39:04Zcom_10630_2254col_10630_37953

Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology. Baglietto-Vargas, David Forner, Stefania Cai, Lena Martini, Alessandra C Trujillo-Estrada, Laura Swarup, Vivek Minh Thu Nguyen, Marie Do Huynh, Kelly Javonillo, Dominic I Minh Tran, Kristine Phan, Jimmy Jiang, Shan Kramár, Enikö A Nuñez-Diaz, Cristina Balderrama-Gutierrez, Gabriela Garcia, Franklin Childs, Jessica Rodriguez-Ortiz, Carlos J Garcia-Leon, Juan Antonio Kitazawa, Masashi Shahnawaz, Mohammad Matheos, Dina P Ma, Xinyi Da Cunha, Celia Walls, Ken C Ager, Rahasson R Soto, Claudio Gutierrez, Antonia Moreno-Gonzalez, Ines Mortazavi, Ali Tenner, Andrea J MacGregor, Grant R Wood, Marcelo Green, Kim N LaFerla, Frank M Alzheimer, Enfermedad de 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 Aβ under control of the mouse App locus. Remarkably, changing 3 amino acids in the mouse Aβ 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 Aβ sequence was flanked by loxP sites we show that Cre-mediated excision of exon 14 ablates hAβ expression, rescues cognition and reduces the formation of PAS granules. 2024-09-27T19:09:59Z 2024-09-27T19:09:59Z 2021-04-23 journal article Baglietto-Vargas, D., Forner, S., Cai, L. et al. Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer’s disease-like pathology. Nat Commun 12, 2421 (2021). https://doi.org/10.1038/s41467-021-22624-z https://hdl.handle.net/10630/33784 10.1038/s41467-021-22624-z eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Springer Nature