Elevated amyloid-β plaque deposition in dietary selenium-deficient Tg2576 transgenic mice

Abstract

Selenium-containing proteins (e.g., glutathione peroxidases) are important antioxidants in neuronal defense against oxidative stress. In this study, the production of amyloid-β (Aβ) plaques in the brain of the Tg2576 transgenic mice was investigated under dietary selenium-deficient conditions. The 16-week-old mice were fed a selenium-deficient diet (0.004 μg-selenium g⁻¹-diet) or a selenium-adequate diet (0.386 μg-selenium g⁻¹ diet) for 76 weeks. The selenium concentrations of the organs/tissues in the selenium-deficient diet-fed mice were significantly decreased in comparison to those in the selenium-adequate diet-fed mice; 1.7% of that in the selenium-adequate diet-fed mice in the liver and 43% of that in the selenium-adequate diet-fed mice in the brain. The Aβ plaques formed in the brain were fluorescently stained with thioflavin T, and then the obtained images of the brain slices were qualitatively analyzed. The feeding of the selenium-deficient diet to the Tg2576 transgenic mice resulted in more than a two-fold increase in the total area of the Aβ plaques in comparison to that of the selenium-adequate diet. The elevated Aβ plaque deposition in the selenium-deficient mice can be explained as a consequence of decrease in the selenium concentration, which suggests that the selenium status is associated with the production and/or the clearance of the Aβ peptide. The selenium-deficiency could possibly promote the onset and/or progression of Alzheimer's disease (AD) dementia, if the Aβ peptides initiate a sequence of events that lead to AD dementia. Consequently, the results shown here suggest that AD has an important relation with the selenium status in vivo.