Aluminium, Mercury and Alzheimer's Disease

Summary

Recent discoveries have established that Alzheimer 's disease can have several different causes- some are inherited and others may arise from the environment. In the majority of cases, both genetic and environmental factors probably work together to cause the disorder.

Click here for more information about the genetics of Alzheimer's disease.

Since 1965, it has been suggested that aluminium is a possible environmental agent contributing to the development of Alzheimer's disease in some people. There is circumstantial evidence linking aluminium with Alzheimer's disease, but no causal link has been proven. Most medical experts are either undecided or consider it unlikely that aluminium plays a significant role.

Mercury is known to be toxic and there is a circumstantial link with Alzheimer's, but again no causal link has been established.

Environmental risk factors in Alzheimer's disease.

In contrast to recent advances in identifying genetic risk factors for Alzheimer's disease, much less is known about environmental factors which may cause the disease. Although aluminium has been repeatedly implicated as a possible candidate, the evidence is circumstantial and the issue has been marked by scientific controversy and inaccurate reporting by the media.

 Aluminium and Alzheimer's

The 'aluminium hypothesis' was first put forward in 1965 when it was shown that injection of aluminium compounds into rabbits caused tangle-like formations in nerve cells. However, these experimental tangles differ in structure and composition from Alzheimer tangles in the human brain.

There are a number of other circumstantial links between aluminium and Alzheimer's disease:

• Aluminium has been shown to be associated with both plaques and tangles in the Alzheimer brain. Some groups have disputed these claims and, in any case, the presence of aluminium does not prove a causal relationship it could be a harmless second secondary association.
• It has been claimed that the brain content of aluminium is increased in Alzheimer's disease. However, a recent study in which a large number of Alzheimer brains were compared with normal brains failed to find any difference in the overall amount of aluminium. This finding does not exclude the possibility that changes in the content of aluminium in specific types of cells (rather than the amount present overall) could contribute to the disease.
• Various investigations have suggested that more people have Alzheimer's disease in areas where the aluminium content in water supplies is highest, but the method and results of these investigations have been questioned. Findings have not been clear enough to warrant changes in the way in which aluminium sulphate is used to remove organic matter from water supplies.
• Furthermore, it has been proposed that any connection between aluminium in water supplies and Alzheimer's disease may be modified by silicon dissolved in the water. Dissolved silicon markedly reduces the absorption of aluminium from the intestine and could in theory be used to protect against exposure to aluminium in the diet.
• Studies of the effects of other sources of aluminium such as tea, antacid and antiperspirant have also failed to show a positive association with Alzheimer's disease.
• People with kidney failure are unable to excrete aluminium and yet they frequently have to be treated with compounds that contain aluminium. Studies of the brains of such patients have shown that aluminium accumulates in nerve cells that are particularly vulnerable in Alzheimer's disease. Moreover, in the same brain regions there are -amyloid deposits and changes in APP and tau protein which resemble those occurring in Alzheimer's disease. It is possible, however, that such changes may reflect other metabolic disturbances caused by kidney failure.
• Treatment with desferrioxamine (DFO), a drug which binds aluminium and removes it from body tissues, has been reported to slow down the decline in abilities of patients with Alzheimer's disease. Unfortunately the effect is small, the drug has to be given by injection into muscle and it also has a major effect on iron stores in the body. Since there is evidence that iron is involved in age-related oxidative damage to tissues, the effects of DFO may have nothing to do with aluminium.
• There have been many experimental studies on animals and in the test tube showing that aluminium has toxic effects on the nervous system or its component chemicals, but in most cases the doses are much higher than those occurring naturally in tissues. Direct effects of aluminium on the aggregation of both - amyloid and tau protein have been reported, but their physiological significance is unclear.

The expert view on aluminium

There have been many conferences on aluminium and health in recent years, organised by the biomedical research community, various regulatory agencies and the aluminium industry. The consensus medical and scientific view is that the findings outlined above do not convincingly demonstrate a causal relationship between aluminium and Alzheimer's disease and that no useful medical or public health recommendations can be made at present. On the other hand, an association between aluminium and Alzheimer's disease cannot be entirely discounted in the face of the various strands of circumstantial evidence.

Further work to resolve this problem is going on, supported by the government, medical research charities and the aluminium industry. These studies are not easy - aluminium is abundant in the environment and exists in many different chemical forms, so exposure is extremely difficult to measure. Despite the widespread presence of aluminium, the majority of elderly people do not get Alzheimer's disease and the risk from this source, if any, must be small.

Just as there is a growing list of genes implicated in Alzheimer's disease so there are likely to be many environmental risk factors which can potentially confuse investigations. One hopeful approach is the development of transgenic animals with some of the pathological features of Alzheimer's disease. It may be possible to determine whether aluminium accelerates the development of pathological changes in these animals.

Clinical studies will become more refined as we identify more genetic risk factors, and we may find that some make people more susceptible to environmental agents. Only if such studies show that aluminium contributes to the development of Alzheimer's disease will medical and public health recommendations to limit exposure be justified.

Mercury and Alzheimer's disease

It is already known that mercury has potent toxic effects on the central nervous system, but there is very little evidence to link this metal with Alzheimer' s disease.

• It has been reported that the brain content of mercury is increased in Alzheimer's disease and further investigations are required to confirm this. But even if confirmed, such a finding does not necessarily indicate a causal relationship.
• Under certain conditions in the test tube, mercury has been shown to block the binding of a compound called GTP to a protein known as tubulin. Similar effects have been obtained with rats made to inhale mercury vapour. Binding of GTP by tubulin is important for normal brain function and it has been claimed that this process is defective in tubulin extracted from Alzheimer brains.

It is likely that medical and media interest in this topic will grow following recent reports that mercury can escape from dental amalgam, and there are moves in several countries to eliminate the use of mercury fillings. However, it should be emphasised that these moves are based on the known toxicity of mercury and not because of the evidence relating to Alzheimer's disease.

The 'threshold hypothesis'

It is worth pointing out that according to the threshold hypothesis , which is accepted by many scientists, any environmental agent which damages the brain could be a risk factor for Alzheimer's disease. The degenerative changes which occur in the brain of someone with Alzheimer's disease almost certainly precede the development of clinical symptoms, perhaps by several years. During this period, the brain is able to call upon reserve capacity until a critical threshold of damage is passed beyond this point the brain is no longer able to compensate and symptoms such as memory problems appear.

Any damage from toxic substances which reduces the reserve capacity of the brain will result in the earlier appearance of clinical symptoms. It is likely that many environmental agents can contribute in a small way to brain damage over the course of a lifetime and it will be extremely difficult to determine if factors such as aluminium or mercury act in this non-specific way.

With special thanks to Professor Jim Edwardson

MRC Neurochemical Pathology Unit Newcastle General Hospital

Westgate Road Newcastle upon Tyne NE4 6BE

November 1995

Page Text supplied by The Alzheimer's Disease Society of Great Britain