P1-116: longitudinal assessment of the relationship between sex differences and cognition in the tgf344-ad rat

Presently, 3.3 of the 5 million Americans with Alzheimer's disease (AD) are women, thus females are disproportionately diagnosed with the disease. AD is hallmarked by progressive memory loss, eventually leading to dementia and death. Studies have shown that the greatest risk factors for AD are age and gender, with females associated with greater risk of the disease. We hypothesize that prodromal AD changes that occur during female reproductive senescence increase vulnerability to cognitive impairment and AD pathogenesis. To assess the relationship between female AD risk and impaired learning and memory, we utilized the novel TgF344-AD rat model. This transgenic rat manifests the full spectrum of AD pathology including age-dependent cerebral amyloidosis, neuroinflammation, neurofibrillary tangles, and neuronal death. In this study, we compared male and female TgF344-AD (Tg) rats to wild-type rats at 5-6, 13-15, and 20–22 months of age on a battery of cognitive tests. Behavioral paradigms included novel object recognition (NOR; a measurement of episodic memory) and Barnes maze (a hippocampus-dependent spatial reference learning and memory task). The goal of the study being to cognitively evaluate two sexes of AD rats before, during, and after development of AD pathological changes. In the NOR task, 13–15 and 20-22-month-old female Tg rats lack the ability to discriminate between novel and familiar objects, demonstrating impaired episodic memory. In Barnes maze, animals undergo two days of reversal following learning and testing phases. In reversal, both aged groups (13-15 and 20-22-months-old) of female Tg rats displayed impaired spatial memory with significantly more errors (P<0.001) vs. male Tg rats. Interestingly, when comparing latency to reach the escape goal during the reversal phase, 13-15-month-old male Tg rats took significantly longer (P<0.05) to complete the task. Yet, at 20–22 months, female Tg rats took longer (p<0.05) than male counterparts to reach the reversal goal. No significant sex differences were observed in the learning phase of the Barnes maze task when considering error or latency measures, suggesting that females do not have impaired spatial learning. Overall results of this study suggest a complex relationship between sex and memory deficits in the TgF344-AD rat model.