Abstract
The overall effect of brain zinc (Zn2+) in the progression and development of Alzheimer's disease (AD) is still not completely understood. Although an excess of Zn2+ can exacerbate the pathological features of AD, a deficit of Zn2+ intake has also been shown to increase the volume of amyloid plaques in AD transgenic mice. In this study, we investigated the effect of dietary Zn2+ supplementation (30 p.p.m.) in a transgenic mouse model of AD, the 3xTg-AD, that expresses both β amyloid (Aβ)- and tau-dependent pathology. We found that Zn2+ supplementation greatly delays hippocampal-dependent memory deficits and strongly reduces both Aβ and tau pathology in the hippocampus. We also evaluated signs of mitochondrial dysfunction and found that Zn2+ supplementation prevents the age-dependent respiratory deficits we observed in untreated 3xTg-AD mice. Finally, we found that Zn2+ supplementation greatly increases the levels of brain-derived neurotrophic factor (BDNF) of treated 3xTg-AD mice. In summary, our data support the idea that controlling the brain Zn2+ homeostasis may be beneficial in the treatment of AD.
Highlights
Zn2 þ is sequestered into the mitochondria[7,8] and mitochondrial dysfunctions as well as energy deficiency are prominent early events in Alzheimer’s disease (AD).[9]
Recent findings in a triple transgenic mouse model of AD indicate a synergistic interaction between amyloid-b peptide (Ab) and h-tau in impairing the oxidative phosphorylation system (OXPHOS) as well as the production of reactive oxygen species.[9]
We investigated the effect of dietary Zn2 þ supplementation on the disease progression of the 3xTg-AD mouse, a transgenic animal model of AD that exhibits both Ab- and tau-dependent pathology
Summary
Zn2 þ is sequestered into the mitochondria[7,8] and mitochondrial dysfunctions as well as energy deficiency are prominent early events in AD.[9] recent findings in a triple transgenic mouse model of AD indicate a synergistic interaction between Ab and h-tau in impairing the oxidative phosphorylation system (OXPHOS) as well as the production of reactive oxygen species.[9] In that respect, we have previously shown the expression of pro-AD factors, such as mutant human presenilin-1 (PS1), amyloid precursor protein (APP) and human h-tau present in 3xTg-AD mice strongly alters intracellular Zn2 þ homeostasis in cultured cortical neurons undergoing oxidative stress.[10]. End points of the study were analysis of cognitive decline, the appearance of intraneuronal Ab and h-tau, AD-related mitochondrial dysfunctions, as well as disruption of the BDNF neurotrophic pathway
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