Baglietto-Vargas, DavidForner, StefaniaCai, LenaMartini, Alessandra C.Trujillo-Estrada, LauraSwarup, VivekNguyen, Marie Minh ThuDo Huynh, KellyJavonillo, Dominic I.Tran, Kristine MinhPhan, JimmyJiang, ShanKramár, Enikö A.Nuñez-Diaz, CristinaBalderrama-Gutierrez, GabrielaGarcia, FranklinChilds, JessicaRodriguez-Ortiz, Carlos J.Garcia-Leon, Juan AntonioKitazawa, MasashiShahnawaz, MohammadMatheos, Dina P.Ma, XinyiDa Cunha, CeliaWalls, Ken C.Ager, Rahasson R.Soto, ClaudioGutierrez, AntoniaMoreno-Gonzalez, InesMortazavi, AliTenner, Andrea J.MacGregor, Grant R.Wood, MarceloGreen, Kim N.LaFerla, Frank M.2024-02-192024-02-192021-04-23http://hdl.handle.net/10668/4585http://hdl.handle.net/20.500.12105/18320The 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.engVoRhttp://creativecommons.org/licenses/by/4.0/Periodic acid-schiffExonCognitionMutationGene expressionAlzheimer diseaseReacción del ácido peryódico de SchiffExonesCogniciónMutaciónExpresión génicaEnfermedad de AlzheimerAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsBrainFemaleGene Expression ProfilingGene OntologyGene Regulatory NetworksHumansMaleMice, Inbred C57BLMice, TransgenicNeuronal PlasticityDisease Models, AnimalMutationMicePeriodic AcidAmino AcidsMobile ApplicationsExonsCognitionGene ExpressionAttribution 4.0 International3389329010.1038/s41467-021-22624-z2041-1723Nature Communicationsopen access