Effects of Increased Dietary Zinc Consumption on Spatial Learning in a Late-Onset Transgenic Mouse Model of Alzheimer’s Disease

Angela Railey

Advisor: Jane Flinn

Committee Members: Craig McDonald, Marge Battaglia, Kathy Mcknight

Research Hall, 91
April 01, 2011, 06:30 AM to 07:30 AM

Abstract:

Alzheimer’s disease (AD) is the most common cause of dementia in the U.S.  Currently much of the research devoted to AD focuses on genetic mutations associated with early-onset AD, which only account for 5-10% of total cases.  Consequentially, treatments developed based on this research may only be effective for a small subset of patients.  In contrast, this project focuses on late-onset AD and addresses the interaction between increased dietary zinc (Zn) consumption and the different isoforms of the Apolipoprotein E (ApoE) gene.  The ApoE4 isoform in particular is overrepresented in late-onset AD and has been shown to enhance Zn binding to the amyloid protein, the key constituent of the extracellular plaques that characterize the disease.  There is increasingly more evidence that Zn may play a central role in the pathogenesis of AD by affecting beta-amyloid (Aβ) aggregation and deposition in the brain.  This study sought to determine if elevated dietary Zn would impair spatial learning, particularly in animals carrying the human APP and ApoE4 genotype.  Wild type (Wt) and transgenic (Tg) mice were administered Zn (10 ppm ZnCO3) in the drinking water for a period of 20 weeks.  Mice were tested in two spatial memory tasks, the Barnes Maze and the Morris Water Maze, at five months of age.  In the Barnes Maze Task, Tg mice showed significant learning deficits in comparison to Wt mice as evidenced by an increased latency to reach the escape box.  Zn-treated mice of the APP/ApoE4 genotype had significantly longer latencies and made significantly more errors than APP/ApoE4 animals maintained on lab water.  These data suggest that increased dietary Zn consumption can significantly impair spatial learning in an APP/ApoE4 transgenic mouse model.  These findings are particularly relevant given that the use of dietary supplements such as Zn is common in the elderly, a population already at risk for AD.  For example, high doses of Zn are currently prescribed for the treatment of Advanced Macular Degeneration.  In individuals with the ApoE4 genotype, increasing Zn intake could have particularly detrimental effects.