# Aluminium and Alzheimer's Disease #
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.
Aluminium and Alzheimer's Disease : The science that describes the link [Hardcover] : C. Exley (Author) Aluminium, neurofibrillary degeneration and Alzheimer's disease. DR Crapper, SS Krishnan : Brain. 1976 Mar. 99(1):67-80. Journal of Alzheimer's Disease. Brain aluminum distribution in Alzheimer's Disease and experimental neurofibrillary degeneration. Science 1973; 180:511-513. Gastrointestinal absorption of aluminum from aluminum-containing antacids:WD Kaehny, AP - N Engl J Med 294:184â€“188, 1976 Krishnan SS, Quittkat S: Aluminum, neurofibrillary degeneration and Alzheimer's disease, Brain 99:67â€“80, 1976 Geographical relation between Alzheimer's disease and aluminium in drinking water: CN Martyn, C Osmond, JA Edwardson, DJP Barkerâ€¦ - The Lancet, 1989 Absence of aluminium in neuritic plaque cores in Alzheimer's disease : JP Landsberg, B McDonaldâ€¦ - 1992 - nature. Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: a laser microprobe (LAMMA) study : PF Good, DP Perl, LM Biererâ€¦ - Annals of [HTML] Metabolism and possible health effects of aluminum.from nih.gov PO Ganrot - Environmental Health Perspectives, 1986 - ncbi.nlm.nih.gov Brain-aluminium concentration in dialysis encephalopathy: JR McDermott, AI Smith, MK Ward, IS Parkinsonâ€¦ - The Lancet, 1978 - Elsevier Aluminium as a risk factor in Alzheimer's disease, with emphasis on drinking water: from anti-cancer.fr TP Flaten - Brain Research Bulletin, 2001 - Elsevier Therapy of Alzheimer's Disease
Aluminium was implicated in plaque formation a number of years ago. Studies found Aluminium in plaque cores stripped of protein in some animals. Earlier studies claimed that tangle-bearing neurones in Alzheimer Disease also contain elevated levels of Aluminium. Aluminium is toxic to the nerve cells , but most Aluminium is excreted by the kidneys and very little crosses the blood brain barrier. In the blood stream plasma, Aluminium is bound to a blood protein which trasfer it to areas were it is excreted or metabolised. Studies to assess risk of dementia in areas with high Aluminium in drinking water have been greatly critised. The accepted view is that Aluminium has no role in causing dementia.
Amyloid was isolated from the brains affected by Alzheimer disease. It recieved the name of Beta-protein, A4-protein or AB. The deposit is filamentous and insoluble forming diffuse plaques. Diffuse plaques is widely distributed throughout many areas of the dementia brain. However, many intellectually intact brains have abundant diffuse plaques. Diffuse plaques are probably not damaging to the brain. Downâ€™s syndrome brains at around age 20 years have diffuse deposits but involvement of the neurones and no Neurofibillary tangles inside the brain cells. Thus, amyloid deposition is taken to be first manifestation of AD pathology.
The amyloid precursor protein (APP) gene is located on chromosome 21. In the brain, APP is made mainly found in neurones. It has been suggested that the formation of amyloid deposits may result from an imbalance in the proportion of APP. Down's cases develop amyloid deposits in their twenties. Down's patients have an extra copy of APP gene on the third copy of chromosome 21. This leads to elevated levels of APP. Down's syndrome patients after age 35 have changes in their brain indistinguishable from Alzheimer's disease.
The dying and loss of brain cells can be evident by the naked eye when examining the brain of someone who died of Alzhiemer's disease. The thickness of coretx brain areas is reduced and the cavities in the brain are larger. This brain atrophy is possibly seen in the living patient if a brain scan or Magnetic Resonance Imaging on the head is performed. There is a degree of brain atrophy with advance of age, though in Alzhiemer's disease the level of atrophy is much greater than expected.