2026-05-20T23:31:58Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/183202024-11-28T14:52:38Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Baglietto-Vargas, David author Forner, Stefania author Cai, Lena author Martini, Alessandra C. author Trujillo-Estrada, Laura author Swarup, Vivek author Nguyen, Marie Minh Thu author Do Huynh, Kelly author Javonillo, Dominic I. author Tran, Kristine Minh author Phan, Jimmy author Jiang, Shan author Kramár, Enikö A. author Nuñez-Diaz, Cristina author Balderrama-Gutierrez, Gabriela author Garcia, Franklin author Childs, Jessica author Rodriguez-Ortiz, Carlos J. author Garcia-Leon, Juan Antonio author Kitazawa, Masashi author Shahnawaz, Mohammad author Matheos, Dina P. author Ma, Xinyi author Da Cunha, Celia author Walls, Ken C. author Ager, Rahasson R. author Soto, Claudio author Gutierrez, Antonia author Moreno-Gonzalez, Ines author Mortazavi, Ali author Tenner, Andrea J. author MacGregor, Grant R. author Wood, Marcelo author Green, Kim N. author LaFerla, Frank M. author 2021-04-23 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. 10.1038/s41467-021-22624-z 2041-1723 Nature Communications http://hdl.handle.net/10668/4585 33893290 http://hdl.handle.net/20.500.12105/18320 Periodic acid-schiff Exon Cognition Mutation Gene expression Alzheimer disease Reacción del ácido peryódico de Schiff Exones Cognición Mutación Expresión génica Enfermedad de Alzheimer Generation of a humanized Aβ expressing mouse demonstrating aspects of Alzheimer's disease-like pathology