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Research & Development News

Aluminum and Mercury can lead to Alzheimers: An Investigation
Mercury and aluminum are considered to be neurotoxic metals, and they are often connected with the onset of neurodegenerative diseases. In this study, mercuric mercury, methylmercury and aluminum were studied in three different cell lines of neural origin. To evaluate the effects, mitochondrial cytotoxicity and apoptosis induced by the metals were measured after various incubation times. SH-SY5Y neuroblastoma, U 373MG glioblastoma, and RPE D407 retinal pigment epithelial cells were subcultured to appropriate cell culture plates and 0.01–1,000 µM concentrations of methylmercury, mercuric and aluminum chloride were added into the growth medium. In the assay measuring the mitochondrial dehydrogenase activity, WST-1, the cultures were exposed for 15 min, 24 or 48 h before measurement. Cells were allowed to recover from the exposure in part of the study. Apoptosis induced by the metals was measured after 6-, 24- and 48-h exposure times with the determination of activated caspase 3 enzyme. Mitochondrial assays showed a clear dose-response and exposure time-response to the metals. The most toxic was methylmercury (EC50 ~0.8 µM, 48 h), and the most sensitive cell line was the neuroblastoma cell line SH-SY5Y. Furthermore, there was marked mitochondrial activation, especially in connection with aluminum and methylmercury at low concentrations. This activation may be important during the initiation of cellular processes. All the metals tested induced apoptosis, but with a different time-course and cell-line specificity. In microscopic photographs, glioblastoma cells formed fibrillary tangles, and neuroblastoma cells settled along the fibrilles in cocultures of glial and neuronal cell lines during aluminum exposure. The study emphasized the toxicity of methylmercury to neural cells and showed that aluminum alters various cellular activities.
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.
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.

Aluminum and Alzheimers

The 'aluminum hypothesis' was first put forward in 1965 when it was shown that injection of aluminum 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.

Mercury and Alzheimers

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.