Phenotypic differences between Alzheimer's disease models expressing human in the developing eye and brain.

expressing amyloid-β42 () transgenes have been used as models to study Alzheimer's disease. Various transgenes with different structures induce different phenotypes, which make it difficult to compare data among studies which use different transgenic lines. In this study, we compared the phenotypes of four frequently used transgenic lines, , , , and . Among the four transgenic lines, only has two copies of the upstream activation sequence-amyloid-β42 () transgene, while remaining three have one copy. has the 3' untranslated region of , while the others have that of SV40. and have the rat pre-proenkephalin signal peptide, while and have that of the fly argos protein. When the transgenes were expressed ectopically in the developing eyes of the flies, transgene resulted in a strongly reduced and rough eye phenotype, while only showed a strong rough eye phenotype; and had mild rough eyes. The levels of cell death and reactive oxygen species (ROS) in the eye imaginal discs were consistently the highest in , followed by , , and . Surprisingly, the reduction in survival during the development of these lines did not correlate with cell death or ROS levels. The flies which expressed or experienced greatly reduced survival rates, although low levels of ROS or cell death were detected. Collectively, our results demonstrated that different AD models show different phenotypic severity, and suggested that different transgenes may have different modes of cytotoxicity. Aβ42: amyloid-β42; AD: Alzheimer's disease; UAS: upstream activation sequence.