Researchers at the University of Washington found that cadmium exposure, combined with a genetic predisposition to Alzheimer’s disease, might accelerate cognitive decline. The researchers arrived at this finding after exposing mice with an Alzheimer’s risk gene to cadmium.  They detailed their findings in a paper published in the journal Toxicological Sciences.

The effects of cadmium plus an Alzheimer’s risk gene

The so-called human apolipoprotein E (APOE) gene codes for a protein called apolipoprotein. This combines with fats to form lipoproteins, which carry cholesterol through the bloodstream. The APOE4 gene is a variant of the APOE gene. It significantly raises a person’s risk of developing Alzheimer’s, which is why it is considered an Alzheimer’s risk gene.

For their study, the researchers wanted to know how being carrier of this gene, combined with exposure to cadmium, affects cognition. Cadmium is a heavy metal that is extremely toxic to the brain. It occurs naturally and is extracted during the production of copper, lead and zinc. Cigarette smoke and polluted air also contain this toxin.

Over a period of 14 weeks, the researchers gave a group of mice with the APOE4 or the APOE3 gene water that contained low doses of cadmium. APOE3 is another variant of the APOE gene. It is widespread, with around half of the population carrying it.

The maximum amount of cadmium that the mice ingested was equivalent to the amount that Americans have in their blood, including people who never smoked.

As part of their experiment, the researchers put the rats through standard novel object location tests and T-maze tests, both of which engage the hippocampus, a region of the brain that is crucial for learning and memory. The hippocampus is one of the brain areas that is damaged the most during the early stages of Alzheimer’s.

The mice that ingested cadmium performed worse in the novel object location tests than untreated mice, indicating poorer short-term spatial working memory. This deficit in memory appeared earlier in mice with the APOE4 gene than those with APOE3, and earlier in males than females with the same genetic makeup.

Later in life, mice with the APOE4 gene performed worse in the T-maze test than those with APOE3. This indicated a reduced tendency to explore new environments and therefore poorer short-term spatial working memory. In addition, the researchers found that cadmium exposure negatively impacts nerve cell development in the hippocampus of male mice with the APOE4 gene.

Cadmium pools in the brain due to Alzheimer’s risk gene

These findings led the researchers to conclude that interactions between the APOE4 gene and cadmium accelerates cognitive decline, with young male mice being more susceptible to this effect than young females. The researchers pointed to impaired nerve cell development in the hippocampus as one of the underlying mechanisms, which possibly occurs because the APOE4 gene lets cadmium into the brain.

“It is possible that APOE4 may cause leakage on the blood-brain barrier and lead to a higher degree of cadmium accumulation in the APOE4 brain,” the researchers wrote.

Zhengui Xia, a professor of toxicology at Washington University and one of the study’s researchers, commented: “Exposure to cadmium through our daily lives could have a detrimental effect on our cognition. If you have the APOE4 gene, the risk is significantly higher.”

“This heavy metal is bad for you,” she added.