The Behavioral Effects of Zinc on Mice Expressing the Human P301L Gene



Kochen, William

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Alzheimer’s disease is the most common form of dementia in the world, being responsible for between 60-70% of all cases of dementia, and is characterized as a chronic progressive neurodegenerative disorder. Patients with Alzheimer’s disease display deficits in many cognitive areas such as memory, depression, and social functioning. Although a diverse number of factors have been considered to play a role in Alzheimer’s disease, the pathology of neurofibrillary tangles is present in all patients with the disease. Neurofibrillary tangles form from hyperphosphorylation of the Tau protein and are responsible for the death of neurons. As tangles spread further in the brain, cognitive deficits increase as well. Another major health issue of discussion is the bodies’ use of biometals such as zinc and copper. Biometals are necessary for healthy body function but must be maintained within a certain healthy range; if problems with homeostasis cause the metal to fall outside of this range, then health problems will occur. The disruption of biometal homeostasis has been implicated in many diseases including Alzheimer’s disease. The levels of zinc and copper in the body are positively related to the amount of neurofibrillary tangles. Despite the large body of work on biometals and Alzheimer’s disease, no study has looked at the cognitive effects of excess zinc in a mouse model containing neurofibrillary tangles. This study examined the behavioral effects of excess zinc on transgenic mice containing the human P301L gene which produces neurofibrillary tangles in the mice. Fifty-two total mice were tested beginning at an age of three and half months old. Behavioral tests ran include a seven day Morris Water Maze paradigm as well as a seven day circadian rhythm assay and a two day nesting paradigm. Tau mice performed significantly worse than wild type mice in time to find the platform, number of platform crossings, thigmotaxis, nesting, and circadian rhythm. Deficits in nesting, circadian rhythm, and time to find the platform were significantly impaired for the transgenic mice drinking zinc water compared to transgenic mice drinking tap water. Tau mice consuming zinc water built the poorest nests and had the longest amount of time to find the platform in Morris Water Maze testing. These findings add to the growing literature on the negative role of zinc in neurodegenerative disorders including Alzheimer’s disease. The elderly population may need to be cautioned about the consumption of excess zinc.


This thesis has been embargoed for 1 year and will not be available until December 2018 at the earliest.


Zinc, Tau, Dementia, Behavior