The present invention addresses the problem of providing a knock-in mouse that develops Osaka-mutation-mediated Alzheimer's disease through gene expression in normal physiological ranges. The problem is solved by a knock-in mouse as described below. A knock-in mouse into which a mutant amyloid precursor protein (mutant APP) gene described in (a) or (b), below, has been introduced, said mouse being homozygous for the mutant APP gene. (a) A mutant APP gene that codes a mutant murine amyloid-&bgr； protein and comprises the amino acid sequence represented by SEQ ID NO: 1. (b) A mutant APP gene that codes a polypeptide which induces the onset of Alzheimer's disease when expressed in mice, said gene comprising the amino acid sequence represented by SEQ ID NO: 1, in which one or more amino acids other than the 5th glutamine residue from the N terminal, the 10th phenylalanine residue from the N terminal and the 13th arginine residue from the N terminal has/have been substituted, deleted, inserted or added.
