An Investigation into the Role of Iron, Copper, and Gender in a Transgenic Mouse Model of Alzheimer's Disease

Caitlin M. Groeber

Advisor: Jane M Flinn, PhD, Department of Psychology

Committee Members: Patrick E. McKnight, Ester Peters

Johnson Center, D
April 22, 2013, 01:00 PM to 10:00 AM


Age-related diseases are more prevalent due to increasing longevity, with this comes increasing dietary supplementation to maintain a healthy lifestyle. Alzheimer’s disease (AD) is the primary cause of dementia and the sixth leading cause of death in the United States. Previous studies of transgenic AD mouse models have found that long-term dietary supplementation of zinc (Zn) impairs spatial memory, while copper (Cu) shows remediation of this impairment. Iron (Fe) shows a similar impairment in these tasks, but the potential effects of remediation by Cu have not been studied. In humans, being female is a risk factor for cognitive impairment in AD, therefore it is important to examine gender differences in AD. To examine the effect and interaction of Fe and Cu on cognitive function, male and female transgenic (Tg)CRND8 and wild-type (Wt) mice were administered enhanced drinking water for 5 months: Fe (10ppm FeNO3), Fe+Cu (10ppm FeNO3 + 0.2ppm CuNO3), Cu (0.2ppm CuNO3), and lab tap water. Assessments included the novel object recognition task (NOR; discrimination task) and the Morris water maze (MWM; spatial memory). Histological analysis was conducted on the brain and liver to examine the plaque load, metal content, CP levels, and amyloid levels in the brains of these mice. In NOR, CRND8 mice showed significantly less object recognition than Wt mice. Females showed significantly more object recognition than males, with a greater difference between Wt females and males that decreased between Tg females and males. This is in agreement with human studies, which show that women are more susceptible to cognitive deficits during the progression of AD. Among Tg mice, those raised on Fe+Cu showed significant impairment compared to lab water animals, indicating that copper in addition to iron can impair learning and memory. In MWM, CRND8 mice showed significant spatial learning deficits compared to Wt mice with an inability to decrease latency across days. A similar trend for gender was seen, where Wt females and males perform similarly in the MWM, but Tg females show an inability to decrease latency. The data suggest that the level of specific metals can change the learning and memory processing. These finding are particularly important concerning gender differenced in AD, where men and women may be impacted differently depending on the type of learning. These findings could play an important role in cognitive interventions for those with a genetic predisposition or diagnosed with AD.