Independently, Hsiao et al.,16 taking a relatively similar approach, overexpressed a human APP transgene containing the Swedish FAD mutation (K670N/M671L). Expression was driven by a hamster prion [prion protein (PrP)] promoter that drives expression widely in the nervous system. These mice, termed Tg2576 mice, expressed human APP at levels more than 5-fold above the levels of the endogenous mouse APP, and Aβ40 and Aβ42 levels increased with age. Like PDAPP mice, Tg2576 mice exhibited age-dependent amyloid deposition, which resulted in thioflavin-S–positive plaques similar to those found in AD, along with gliosis and dystrophic neurites. Plaque amyloid was first clearly seen by 11 to 13 months, eventually becoming widespread in cortical and limbic structures. Water maze learning, a test of spatial memory in mice, was normal in 3-month-old animals but impaired in 9- to 10-month-old mice. The Tg2576 mouse line has been made widely available and has been the most widely studied transgenic AD model.
