Behavioral characterization of the Tg2576 transgenic model of Alzheimer's disease through 19 months

Abstract

Behavioral characterization of Alzheimer's disease (AD) transgenic models over multiple time points during aging has been largely inadequate, usually being limited to one or two cognitive-based tasks. In this context, the present study utilized a comprehensive 6-week behavioral battery to characterize sensorimotor and cognitive performance of Tg2576 AD transgenic (Tg +) mice and nontransgenic (Tg −) controls aged 3, 9, 14, and 19 months. Compared collectively to Tg − mice over all four time points, Tg + mice were impaired in Y-maze spontaneous alternation, visible platform recognition, and several sensorimotor tasks; Tg + mice also showed an overall increase in activity measures. The deficits in visible platform became evident by 9 months of age, while those in sensorimotor tasks became clearly manifest by 14 months. Although the behavioral impairments exhibited by Tg + mice were usually progressive through 19 months, Tg − animals also showed similar progressive decline in the same behavioral measures; thus, no task revealed a progressive behavioral decline exclusive to Tg + mice. Moreover, although the 6-week behavioral battery included six cognitively based tasks (i.e., Y-maze, visible platform, Morris water maze, circular platform, passive avoidance, and active avoidance), behavioral analysis through 19 months revealed Tg + mice to be impaired in only the Y-maze and visible platform tasks. Consequently, Tg2576 mice do not exhibit widespread, profound cognitive impairment, even into old age. This may reflect their predominant C57BL/6 background and an apparent inability of the mutant transgene to profoundly alter performance therein.