The Effect of Zinc Status on Cognitive and Vascular Function in a Mouse Model of Alzheimer's Disease

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Isakharov, Lazar N.
Molina, Yamila R.

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Abstract

Exploring potential treatments for Alzheimer’s disease (AD) is important as the aging population continues to increase (Cummings, 2004). A hallmark of AD is excessive oxidative stress (Cheignon et al., 2018). Previous research has identified zinc as an antioxidant and regulator of vasodilation, associatedpositively and negatively with cognitive function (Betrie et al., 2021; Cuajungco & Fagét, 2003). However, its relationship with vasodilation in AD has not been fully elucidated. We hypothesize that maintaining zinc status will improve cognitive and vascular function in a mouse model of AD. We treated male and female AD model mice (6 m) with zinc-normal (30 ppm), low (2-5 ppm) and high (300 ppm) diets for 2 m. We evaluated cognition through rotarod and nest building tests. We assessed large artery stiffness by pulse wave velocity and cerebrovascular function by pressure myography. There was an interaction effect of zinc status and sex (p=0.047) and a main effect of sex (p=0.02) on time spent on rotarod. There was no effect of zinc status or sex on nest building. We identified a main effect of sex on pulse wave velocity (p=0.01). We are still analyzing cerebrovascular function but preliminary results indicate sex-differences in response to zinc diets, where low zinc may be detrimental to males but not females (p<0.05). We find that zinc status may impact cognitive and cerebrovascular function, indicating the need for further research into zinc’s effect on AD. This research is aimed at determining potential future nutritional interventions for reducing the risk of AD.

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Zinc, Alzheimer's Disease, Cardiovascular, Cognition, Nutrition

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