Arsenic, cadmium, and lead: A toxic trinity of risk factors for Alzheimer’s disease?

ResearchBlogging.orgA modern cause of Alzheimer’s disease may lie in the ancient poisons of arsenic, lead, and cadmium. Indian researchers recently reported that young rats exposed to water contaminated with these toxic metals developed symptoms of Alzheimer’s disease, a form of dementia affecting more than 25 million people worldwide. Disturbingly, rats which drank water contaminated with all three metals–water similar to that drank by many Indian people–developed much worse symptoms than rats which drank water with fewer metals. The researchers cautioned that people who drink contaminated water during childhood may develop symptoms of Alzheimer’s disease decades earlier than normal.

How do three ancient poisons work together to create such a potent brew? To tease out the answer, the researchers examined the toxic effects of each metal alone, and the effects of different combinations. Compared to arsenic and cadmium, lead provoked the rats’ brains to make more amyloid-beta–the sticky protein which congeals into plaques in the brains of Alzheimer’s patients. Rats which consumed lead with arsenic had even more amyloid-beta. But when rats consumed lead with arsenic and cadmium, the three metals acted synergistically–the toxic equivalent of shouting into a bullhorn hooked up to an amplifier. The metals amplified each other’s damage to the rats’ brains, and even caused the brains to become inflamed.

With their damaged brains, the rats were worse at figuring out a maze. They were losing their ability to learn and remember–just like humans with Alzheimer’s disease.

Citation:
Ashok A, Rai NK, Tripathi S, & Bandyopadhyay S (2014). Exposure to As-, Cd-, and Pb-Mixture Induces Aβ, Amyloidogenic APP Processing and Cognitive Impairments via Oxidative Stress-Dependent Neuroinflammation in Young Rats. Toxicological sciences : an official journal of the Society of Toxicology PMID: 25288670

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Lead and Alzheimer’s disease: a dangerous combination

Health vs Alzheimers brain

Alzheimer’s disease (AD) causes memory loss and dementia as the brain atrophies. Image from NIH Medline Plus.

Like my grandmother, about 5.4 million Americans suffer from Alzheimer’s disease–a terrible illness that inflicts memory loss and dementia on people as their brains accumulate microscopic plaques and tangles of protein. Despite decades of research, we still don’t know what causes most cases of Alzheimer’s. However, American and Emirati researchers are using mice to investigate a potential cause: exposure during infancy to lead, a toxic element banned from gasoline since 1995. By better understanding how lead causes the microscopic tangles of protein in mouse brains, the researchers hope to identify future drug targets for treating Alzheimer’s disease.

To investigate the link between lead and Alzheimer’s, the researchers exposed mice to lead at different life stages. Some mice consumed lead during infancy, while others drank lead-contaminated water as adults. Still others were exposed as both infants and adults.  Two years later, when the mice were elderly, the researchers compared the brains of the lead-exposed mice to others never exposed to lead. They found that the mice exposed in infancy had more of the tangled protein, tau, compared with the unexposed mice and those only exposed as adults. But there wasn’t simply more tau: a greater proportion of tau was attached to phosphate, an important chemical used by the body.

People with Alzheimer’s also have too much phosphate-covered tau–and the more phosphate-covered tau a person has, the worse their dementia. The researchers suggest that investigating how the body controls the amount of tau in the brain, and how much phosphate attaches to it, will be important for understanding Alzheimer’s and identifying new areas for drug development.

Although my grandmother died several years ago from Alzheimer’s, new research like this makes me hopeful for myself and others at risk of Alzheimer’s–and very, very glad that lead has been banned from gasoline in the United States.