(A) To verify that the humanizing mutations were correctly inserted into App exon‐16, exon-16 was amplified by PCR from Appw/w and Apph/h rats. PCR products’ sequencing showed correct insertion of the humanizing mutations into the Apph/h genome. Nucleotides (G to C, T to A, and GC to AT) and amino acids (G to R, Y to F, and R to H) substitutions are in red. (B) The human Aβ-region specific antibody 6E10 detects Aβ40 and Aβ42 in Apph/h but not Appw/w rats’ brains. Conversely, the rat/mouse Aβ-region specific antibody M3.2 detects Aβ40 and Aβ42 in Appw/w but not Apph/h rats’ brains. (C) Western blot analysis of brain lysates shows that 6E10 detects APP in Apph/h but not Appw/w rats. Conversely, M3.2 detects APP in Appw/w but not Apph/h rats. (D) Apph/h rats do not show AD‐like histopathology at 14 months of age. Six male and six females rats were studied. The figure shows representative IHC in a representative male and female subject. The AT8 samples are not shown because no signal was detected.