Changes in gut, liver may contribute to Alzheimer’s disease susceptibility
NIEHS-funded researchers determined how changes in the gut and liver may contribute to cadmium-induced Alzheimer’s disease (AD). They previously showed that male mice with a genetic variant called apolipoprotein E4 (ApoE4), a known risk factor for AD, were most susceptible to the disease following cadmium exposure. Here, they shed light on how cadmium and ApoE4 alter the gut and liver in ways that may promote AD.
The study included one group of mice genetically altered to have the human ApoE4 gene and another group with the more common human ApoE3 gene variant, which is not implicated in AD. For 14 weeks, the researchers exposed mice to cadmium in drinking water. Then they used genetic sequencing to characterize changes in the gut microbiome and quantified changes in serum metabolite levels and gene expression in the liver.
ApoE4 males exposed to cadmium had the most prominent changes in the gut microbiome, serum metabolites, and gene expression in the liver. Specifically, they had an increase in gut microbial species common in patients with AD. They also had lower lactate-producing bacteria and decreased serum lactate, a molecule essential for neuron function. These animals also showed a positive correlation between inflammation genes in the liver and pro-inflammatory bacteria in the gut.
Study results suggested that cadmium induced changes in the gut and liver of mice most susceptible to AD, notably males with the ApoE4 genetic risk factor. According to the authors, these gut-liver changes may contribute to differences in susceptibility to cadmium-induced AD.
Citation: Zhang A, Matsushita M, Zhang L, Wang H, Shi X, Gu H, Xia Z, Cui JY. 2021. Cadmium exposure modulates the gut-liver axis in an Alzheimer's disease mouse model. Commun Biol 4(1):1398.