Table of Contents
Aluminium is present in the earth's crust in huge amount, mainly in the form of insoluble aluminium silicates. It is scarce in the human body which contain only 30-50 mg of that metal. This is due to the insolubility of aluminium, the presence of a barrier in the gastro-intestinal tract to soluble forms of aluminium, and the ability of the kidneys to excrete aluminium effectively in healthy people.
Aluminium is present in food occurs in additives, tea which is rich in aluminium, and drinking water which is treated with aluminium to remove organic residues. Aluminium is also present in large amounts in medications such as antacids or compound aspirin products.
Most of the aluminium in plasma is bound to the iron-transporting protein transferrin. Aluminium accumulates in areas of the brain with the highest concentration of transferrin receptors such as the cortex, hippocampus and amygdala; the same areas vulnerable to the development of Alzhiemer disease. The distribution of Aluminium in the brain reflects the neurones with the highest requirements for iron. The entry of aluminium into the brain mediated through transferrin.
The issue of aluminium as cause for Alzheimer's disease has been contentious. In special circumstances such as renal failure and massive exposure to aluminium in certain occupations aluminium may cause brain pathology similar to Alzheimer Disease. However, there is no definite evidence of the role of this metal in the causation or development of Alzheimer disease. Some cases of Presenile Alzheimer disease (occurring before the age of 65) run in families and are associated with mutation in the beta-amyloid precursor protein (APP) gene implicated in Alzheimer Disease. Elderly cases of Alzheimer disease are usually sporadic. Twins with typical genes (monozygotic twin pairs) do not share the same chance of developing Alzheimer disease, which provide evidence that environmental factors are highly important in the incidence of Alzheimer disease.
Injecting laboratory animals like rabbits with aluminium salts results in appearance of extensive neurofibrillary changes in the spinal cord and various cortical regions. Similar changes are evident in cats treated in this way, which show cognitive deficits. The proposal that Aluminium is responsible for brain changes in Alzheimer disease gained support from studies that have shown increased level of Aluminium in the neocortex of patients with Alzheimer disease in levels similar to that causing brain pathology in laboratory animals. Another support to the Aluminium hypothesis came from dementia seen in patients who undergo dialysis due to renal failure.
However, there are basic difficulties in explaining the available information from research studies on the role of Aluminium in development of Alzheimer disease. The neurofibrillary changes seen in animals treated with Aluminium is different from the characteristic of tangles of Alzheimer disease formed mainly of double helix filaments of the microtubule-associated tau protein. In addition, the neurofibrillary tangles are not found extensively in the spinal cord in Alzheimer disease. Animals exposed to Aluminium treatment do not develop neuritic plaques of the beta-amyloid.
In the progressive dementia that develops in prolonged dialysis there are focal neurological signs not found in Alzheimer disease and there is no presence of senile plaques and neurofibrillary tangles.
Further suggestions that Aluminium is involved in the causation of Alzheimer disease came from claims that Aluminium accumulates in areas of the brain which are particularly susceptible to develop Alzheimer disease or that transport of Aluminium is faulty in those patients who develop dementia. Other studies have suggested that there is an association between Aluminium and the presence of senile plaques and neurofibrillary tangles. The presence of deposits of premature b-amyloid protein in the brain of patients who undergo chronic renal dialysis; and some evidence that treatment of patients with the chelating agent desferrioxamine can slow down the process of cognitive decline in Alzheimer disease.
The presence of senile plaques and neurofbrillary tangles in the affected brain is diagnostic for Alzheimer disease. This is not a consistent or a specific finding in brains exposed to accumulation of aluminium. The presence of aluminium does not prove that it has a role in development of plaques or tangles. Some studies found that chronic accumulation of aluminium is associated with increased amounts of b-amyloid either due to increased synthesis or abnormal processing of the Amyloid Precursor Protein. It is unlikely that aluminium plays a direct role in the formation of Neurofibrillary tangles as studies did not report cortical tangles in any of the patients who had chronic renal dialysis.
Studies investigated excessive use of antacid as risk for development of Alzheimer disease and found no evidence that amounts of aluminium ingested could represent a significant risk. On the other side, exposure to Aluminium in water in some studies was a risk factor although other studies did not confirm this. A high level of silicic acid may prevent the absorption of aluminium from water and dietary sources. Heavy exposure to aluminium in industries such as mining showed evidence of cognitive decline which depends on the density of exposure.
Another test of this hypothesis suggested that removal of aluminium by a chelating agent may reduce progression of alzheimer disease if aluminium has a significant role in development and progress of this disease. One such study reported that use of injections of a chelating agent desferrioxamine for 24 months has shown 50% reduction in decline of daily living skills in Alzheimer patients. However, the improvement may be due to reduction of the iron-mediated free radical formation.