Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer's disease: three key timepoints through middle-age in females

The Tg F344 rat model of Alzheimer's disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (Afl) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The current experiment evaluated spatial working and reference memory performance, as well as several physiological markers of health, at 3 key age points in female TgF344-AD rats: 6-months, 9-months, and 12-months. At 6 months of age, indications of working and reference memory impairments were observed in transgenic (Tg) rats on the water radial-arm maze, a complex task that requires working and reference memory simultaneously; at 12 months old, Tg impairments were observed for two working memory measures on this task. Notably, no impairments were observed at the 9-month timepoint on this maze. For the Morris maze, a measure of spatial reference memory, Tg rats demonstrated significant impairment relative to wildtype (WT) controls at all 3 age-points. Frontal cortex, entorhina I cortex, and dorsal hippocampus were evaluated for A beta(1-42) expression via western blot in Tg rats only. Analyses of A beta(1-42) expression revealed age-dependent increases in all 3 regions critical to spatial learning and memory. Measures of physiological health, including heart, uterine, and body weights, revealed unique agespecific outcomes for female Tg rats, with the 9-month timepoint identified as critical for further research within the trajectory of AD-like behavior, physiology, and pathology.

Automated summary

The Tg F344 rat model of Alzheimer's disease (AD) exhibits age-dependent neuropathological features and impairments in spatial learning and memory. This study found that Tg rats showed working and reference memory impairments in the water radial-arm maze task at 6 months of age, and working memory impairments at 12 months. Additionally, Tg rats demonstrated significant impairments in spatial reference memory in the Morris maze task at all 3 age points. Western blot analysis showed age-dependent increases in A beta(1-42) expression in key brain regions associated with spatial learning and memory. Physiological measures revealed unique outcomes in female Tg rats at 9 months of age. Overall, the 9-month timepoint was identified as critical for further research on AD-like behavior, physiology, and pathology.