Affiliations: [a] Department of Psychology, George Mason University, Fairfax, VA, USA | [b] Department of Psychology & Counseling, University of the District of Columbia, Washington, DC, USA | [c] Institute for Brain Aging and Dementia, University of California, Irvine, Irvine, CA, USA | [d] Mental Health Research Institute of Victoria, Parkville, VIC, Australia | [e] Water Resources Discipline, United States Geological Survey National Center, Reston, VA, USA
Correspondence:
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Corresponding author: Dr. Jane M. Flinn, Department of Psychology, George Mason University, Mail Stop 3F5, 4400 University Drive, Fairfax, VA 22030, USA. Tel.: +1 703 993 4107; Fax: +1 703 993 1359; E-mail: jflinn@gmu.edu.
Abstract: There is considerable evidence suggesting that metals play a central role in the pathogenesis of Alzheimer's disease. Reports suggest that elevated dietary metals may both precipitate and potentiate an Alzheimer's disease phenotype. Despite this, there remain few studies that have examined the behavioral consequences of elevated dietary metals in wild type and Alzheimer's disease animals. To further investigate this in the current study, two separate transgenic models of AD (Tg2576 and TgCRND8), together with wild type littermates were administered 10 ppm (0.153 mM) Zn. Tg2576 animals were maintained on a zinc-enriched diet both pre- and postnatally until 11 months of age, while TgCRND8 animals were treated for five months following weaning. Behavioral testing, consisting of “Atlantis” and “moving” platform versions of the Morris water maze, were conducted at the end of the study, and tissues were collected for immunohistochemical analysis of amyloid-β burden. Our data demonstrate that the provision of a zinc-enriched diet potentiated Alzheimer-like spatial memory impairments in the transgenic animals and was associated with reduced hippocampal amyloid-β plaque deposits. Zinc-related behavioral deficits were also demonstrated in wild type mice, which were sometimes as great as those present in the transgenic animals. However, zinc-related cognitive impairments in transgenic mice were greater than the summation of zinc effects in the wild type mice and the transgene effects.
