The Neuropathological Effects of Zinc and Copper Supplementation on a Dual Transgenic (hAPP/htau) Mouse Model of Alzheimer’s Disease



Hoyos Justiniano, Rafael

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An imbalance of metals in the brain have shown to influence Alzheimer’s Disease (AD) neuropathology and behavioral deficits both in mice and humans. Previous studies have shown that excess zinc supplementation exacerbates AD neuropathology and behavioral deficits. One reason for this could be that an excess of zinc may lead to a copper deficiency which results in neurological and behavioral problems. This study investigated the neuropathological effect of zinc+copper supplementation on a dual transgenic (hAPP/htau) mouse model of AD. Wildtype and dual transgenic mice were given regular lixit, zinc, and zinc+copper water. The relative density of AD related proteins in the brain were semi-quantified via western blotting. Amyloid and tau accumulation per brain region was assessed through histological analyses. The results of this study showed that wildtype mice showed higher levels of free zinc in the brain than the dual transgenic mice. A significant amount of this free zinc was found in hippocampal regions. Dual transgenic mice on zinc+copper water showed significantly fewer amyloid plaques and significantly more tau tangles than dual transgenic mice on regular lixit and zinc water in specific brain regions. A significantly greater number of plaques and tangles were seen in cortical regions compared to hippocampal regions. This suggests that zinc+copper supplementation may ameliorate amyloid pathology but exacerbate tau pathology in AD mice and that zinc may bind to misfolded AD proteins resulting in less free zinc.



Copper, Tau, Amyloid, Zinc, Alzheimer's Disease, Dual Transgenic Mice