Transgenic rodents harboring APP allele having Swedish mutation

A method of screening an agent for use in treating Alzheimer's disease, comprising:

• forming a plurality of transgenic rodents comprising a diploid genome encoding a human APP polypeptide having the Swedish mutation wherein the amino acid residues at positions corresponding to positions 595 and 596 in human APP695 are asparagine and leucine, respectively,
• selecting one of the transgenic rodents wherein the transgene is expressed to produce a human APP polypeptide having the Swedish mutation, and wherein said polypeptide is processed to ATF-betaAPP in a sufficient amount to be detectable in a brain homogenate of said transgenic rodent
• contacting the selected transgenic rodent with the agent at a dosage of from 1 ng/kg to 10 mg/kg;
• monitoring the cleavage of the amyloid precursor protein polypeptide between the N-terminus of the β-amyloid peptide and the ATF-betaAPP in the contacted transgenic rodent compared to the cleavage in a control transgenic rodent to indicate the agent affects the cleavage.