AβPP-overexpressing transgenic rat model of Alzheimer's disease utilizing the Tg2576 mouse protocol.

The current study examined behavioral and histological effects of amyloid-beta (A beta) protein precursor (A beta PP) overexpression in transgenic (Tg) rats created using the same gene, mutation, and promoter as the Tg2576 mouse model of Alzheimer's disease (AD). Male Tg(+) rats were bred with female wild-type rats to generate litters of hemizygous Tg(+) and Tg(-) offspring. Tg(+) rats and Tg(-) littermates were tested for memory deficits at 4, 8, and 12 months old using a water-maze procedure. There were no significant behavioral differences between Tg(+) rats and Tg(-) littermates at 4 months old but there were significant differences at 8 and 12 months old, and in probe trials at 8 and 12 months old, the Tg(+) rats spent significantly less time and covered less distance in the platform zone. Under acquisition of a fixed consecutive number schedule at 3 months old, Tg(-) littermates demonstrated a longer latency to learning the response rule than Tg(+) rats; while this might seem paradoxical, it is consistent with the role of overexpression of A beta PP in learning. Histological analyses revealed activated astrocytes in brains of Tg(+) rats but not Tg(-) littermates at 6 months old, and thioflavin-S positive staining in the hippocampus and cortex of 17-month old Tg(+) rats but not Tg(-) littermates. Quantification of A beta load in the brain at 22 months indicated high levels of A beta(38), A beta(40), and A beta(42) in the Tg(+) rats. These data suggest this model might provide a valuable resource for AD research.