Metals and the body
Naturally-occurring metals and Alzheimer's disease
Metals such as zinc, copper and iron are present naturally in our bodies. Small amounts of these metals are essential to keeping our brains and bodies working properly. They are involved in many different processes including energy production, the movement of oxygen and the creation and management of many important molecules in the body.
Metals within food
Along with these essential metals, there are other metals that we are exposed to through things such as food.
The body is able to tolerate these metals in small amounts by clearing through the kidneys. These include aluminium and lead, for example it has been shown that if they are not taken out by the kidneys through organ failure or by exposure to extremely high doses these metals are able to deposit in the brain.
These metals are known to cause negative effects in the brain and have been implicated in several neurological conditions.
Copper, zinc and iron
Copper has been the most extensively studied of the natural metals in the brain, but there have also been several studies on exposure to excess zinc and iron among others.
High levels of iron were first reported in the brains of people with Alzheimer's disease in 1953. Since that time it has been shown that iron, as well as zinc and copper are associated with the hallmark Alzheimer's proteins amyloid and tau in the brain.
These hallmark proteins appear as clumps called amyloid plaques and tau tangles in the brains of people with Alzheimer's and are thought to cause damage.
Laboratory experiments using cells in a dish or animal models have shown that copper, zinc and iron can cause the development of these plaques and tangles. However, this doesn't necessarily mean they cause disease.
Zinc has actually been shown to reduce the toxic effect of the amyloid plaques by changing the amyloid proteins into a shape that is less harmful to the brain.
Reactive oxygen species
Copper and iron, but not zinc, have also been implicated in the development of something called'reactive oxygen species' (ROS) in the brain. These are oxygen molecules that have been altered by a chemical reaction. Increased levels are known to be damaging, contributing to cell ageing and death. This is why antioxidants, which can clear up these ROS, are thought to be beneficial to general health.
ROS are believed to be an early contributor to the mechanisms underlying Alzheimer's disease development. Increased levels have been seen in the brains of people with Alzheimer's and toxic amyloid has been shown to increase ROS production.
Conversely, zinc has been shown to protect against ROS by binding to amyloid protein in the place of copper, which reduces the creation of these reactive oxygen species.
The management of the levels of these and other naturally occurring metals is very tightly controlled by the body. It includes many different molecules and disruption of these processes can occur for various reasons. It is not yet clear if the increase in metals seen in the brains of people with Alzheimer's causes the disease. However, it does appear that there is a relationship between the naturally occurring metals and Alzheimer's disease.
Aluminium
In 1965, researchers found that rabbits injected with an extremely high dose of aluminium developed toxic tau tangles in their brains. This led to speculation that aluminium from cans, cookware, processed foods and even the water supply could be causing dementia. The ability of this high dose aluminium to induce tau tangles, increase amyloid levels and contribute to the development of plaques has been shown in laboratory experiments on animals.
Importantly, these results were only seen with extremely high exposures that far exceed the levels that can enter the body through food or potentially through contact with aluminium cookware.
Since this study was reported, much research has been done on the relationship of aluminium and Alzheimer's disease. As yet no study or group of studies has been able to confirm that aluminium is involved in the development of Alzheimer's disease.
Aluminium is seen in the normal, healthy brain. It is not clear how aluminium is getting into the brain from the blood. The levels currently seen in peoples brains hasn't been shown to be toxic but an ageing brain may be less able to process the aluminium. Although aluminium has been seen in amyloid plaques there is no solid evidence that aluminium is increased in the brains of people with Alzheimer's disease. No convincing relationship between amount of exposure or aluminium in the body and the development of Alzheimer's disease has been established.
Aluminium in food and drink is in a form that is not easily absorbed in to the body. Hence the amount taken up is less than 1% of the amount present in food and drink. Most of the aluminium taken into the body is cleaned out by the kidneys. Studies of people who were treated with contaminated dialysis have shown an increase in the amount of aluminium in the brain. This was believed to be as a result of inadequately monitored dialysis which then led to encephalopathy related dementia.Methods of dialysis have since been improved and doctors are better able to predict and prevent this form of dementia.
One large recent study did find a potential role for high dose aluminium in drinking water in progressing Alzheimer's disease for people who already have the disease.
However, multiple other small and large scale studies have failed to find a convincing causal association between aluminium exposure in humans and Alzheimer's disease.
Treatments
The idea that metals could be contributing to Alzheimer's disease has led researchers to study the effects of drugs which remove or inactivate metals in the brain on disease progression. To date, several different drugs have been trialled to see if they can remove excess copper or zinc from the brain or the amyloid plaques.
Many of these drugs have shown positive results in human trials on either reducing plaques and/or cognitive decline. However, as yet, none of these drugs have been approved for use in people due to significant side effects such as severe headaches, renal failure, or life threatening low calcium, among others. Research in to this potential treatment is ongoing.
