Aluminum in brain

LAMMA has been utilized for the analysis of aluminum in brain tissue affected with Alzheimer s disease (Lovell et al. 1993). This new analytical technique of nuclear microscopy can simultaneously image and analyze features in unstained and untreated tissue sections, and therefore avoids contamination problems associated with tissue prepared using conventional chemical techniques. LAMMA was used in a study... 

Zatta P, Favarato M, Nicolini M. 1993. Deposition of aluminum in brain tissues of rats exposed to inhalation of aluminum acetylacetonate. NeuroReport 4 1119-1122. 

Alzheimer s disease Is one of the senile dementias in fact. It Is estimated that 70% of the people who have senile dementia have a form of Alzheimer s disease. The cause and treatment of Alzheimer s disease Is therefore of utmost importance. Crapper and his collaborators at the University of Toronto have reported that autopsies of Alzheimer s patients reveal an accumulation of aluminum Ions in localized areas of the brain (1 ). They also studied the effect of intracranially injecting experimental animals with aluminum, and they found that cats so treated accumulate aluminum In brain cells In concentrations similar to those found In Alzheimer s disease (2). These animals also exhibit structural alterations In brain cells that are similar but not identical to the alterations in Alzheimer s disease. 

The aforementioned findings involve studies in less than 20 patients with dialysis dementia (Farrar et al., 1990) and five with chronic renal failure treated with hemodialysis. More such studies are needed before it can be conclusively stated that the distribution of aluminum in brains of patients with dialysis dementia is not similar to that in patients with Alzheimer s disease. In patients with chronic renal failure without dialysis dementia, neurofibrillary changes have not been found. 

Farrar G, Altmann P, Welch S, Wychrij O, Ghose B, Lejeune J, Corbett J, Prasher J Blair JA. (1990). Defective gallium-transferrin binding in Alzheimer disease and Down syndrome Possible mechanism for accumulation of aluminum in brain. Lancet 335, 747-750. 

Because of numerous similarities in their properties and reactions, aluminum and beryllium will be described together even though they are in different groups of the periodic table. Although it is not completely understood, there is some indication that the accumulation of aluminum in the brain may have some relationship to Alzheimer s disease, and beryllium compounds are extremely toxic. 

The cause of AD is unknown although many hypotheses abound. The gene for one of the excessive amyloid proteins(b-type) has been associated with chromosome 21 at a point not far from a locus linked to some cases of familial Alzheimer s. Victims of Down s syndrome have an extra copy of chromosome 21 and usually fall prey to AD in their 4O s should they live to that age. However no all AD victims have a 21 mutation. Other causative theories involve accumulations of aluminum in the brain or the presence of a slow virus or an infectious protein substance called a prion. 

The toxicity of aluminum has been recognized most clearly by the development of bone disease caused by deposition of A1 in bones of patients on hemodialysis and in infants on intravenous therapy/ 6 Excessive A1 in the water used for dialysis may also cause brain damage. Dietary aluminum may be one cause of Alzheimer s disease/ h but this is controversial as is a possible role of aluminum in vaccines in causing inflammation in muscle.1) Solubilization of soil aluminum by acid rain has been blamed for the decline of forests in Europe and North America,) for the death of fish in acid waters,k and for very large reductions in yield for many crops/ An aluminum-resistant strain of buckwheat makes and secretes from its roots large amounts of oxalate which binds and detoxifies the Al3+ ions. ... 

Alzheimer s disease (AD) is the most prevalent form of senile dementia. Up to two million people in North America suffer from it, and it is the fourth cause of death in the elderly. The cause and treatment of this disease are therefore extremely important. Although the role of aluminum in AD and its in vivo chemistry is not known in detail, patients with Alzheimer s disease have been shown to have elevated aluminum concentrations in certain parts of the brain. Aluminum appears to concentrate in the nucleus. Crosslinks with DNA strands have been found. Crosslink formation can be reversed by sequestering the aluminum with EDTA. 

Aluminum may be a compounding factor in AD it may accelerate or alter the course of the disease via deregulation of calcium. Calmodulin (a protein with four binding sites) activates a number of enzymes and is an important messenger in brain cells. A1 binds to this protein with ten times the affinity of Ca, and changes its conformation. 

Exposure to aluminum is usually not harmful. Aluminum occurs naturally in many foods. Factory workers who breathe large amounts of aluminum dusts can have lung problems, such as coughing or changes that show up in chest X-rays. The use of breathing masks and controls on the levels of dust in factories have eliminated this problem. Some workers who breathe aluminum dusts or aluminum fumes have decreased performance in some tests that measure functions of the nervous system. Some people who have kidney disease store a lot of aluminum in their bodies. The kidney disease causes less aluminum to be removed from the body in the urine. Sometimes these people developed bone or brain diseases that doctors think were caused by the excess aluminum. Some studies show that people exposed to high levels of aluminum may develop Alzheimer s disease, but other studies have not found this to be true. We do not... 

Children may be exposed to high levels of aluminum in drinking water. Brain and bone disease have been seen in children with kidney disease. Bone disease has also been seen in children taking some medicines containing aluminum. Animals exposed to aluminum appeared weaker and less active in their cages, and some movements appeared less coordinated than animals not exposed to aluminum. In addition, aluminum also made some animals unusually sensitive to high temperature. These effects are similar to those seen in adults. It does not appear that children are more sensitive than adults. 

Other intermediate-duration oral studies in rats evaluated effects of aluminum on brain chemistry as well as neurobehavioral performance. Rats that consumed 51 mg Al/kg/day as aluminum chloride in drinking water for 180 days had alterations in behavior (reduced spontaneous locomotor activity, impaired learning, extinction and relearning of an active avoidance task, impaired maze relearning ability) and brain chemistry (increased lipid peroxidation, decreased activity of Na+-, K+-, and Mg2+-ATPases) (Lai et al. 1993). Ingestion of 490 mg Al/kg/day as aluminum sulfate in drinking water for 4-12 weeks caused reduced retention of a learned passive avoidance task and changes in brain chemistry (e.g., increased cyclic adenosine monophosphate levels, decreased concentrations of MAP-2 and other structural... 

Information on chronic oral neurotoxicity of aluminum in animals is limited to a 20 month diet study in mice which found no histopathologic changes in the brain following ingestion of estimated doses as high as 979 mg Al/kg/day as dietary aluminum potassium sulfate (Oneda et al. 1994). These doses do not include aluminum in the base diet. 

There is relatively good agreement in the published literature that the normal level of aluminum in the human brain ranges from 0.25 to 0.75 mg/kg w/w, with gray matter containing about twice the concentration found in the white matter (Alfrey et al. 1976 Arieff et al. 1979 McDermott et al. 1978). 

In rabbits given a single intravenous dose of aluminum lactate, aluminum concentrations did not increase above controls in the cerebellum, white brain tissue, hippocampus, spinal cord, adrenal glands, bone, heart, testes, or thyroid (Yokel and McNamara 1989). Treated animals did have significant increases of aluminum in the liver, serum, bile, kidneys, lungs, and spleen. The liver of exposed rabbits had over 80% of the total body burden of aluminum. Persistence of aluminum in the various tissues, organs, and fluids varied. Estimated half-times of aluminum were 113, 74, 44, 42, 4.2, and 2.3 days in the spleen, liver, lungs, serum, renal cortex, and renal medulla, respectively. The kidneys of treated rabbits also demonstrated a second half-time which exceeded 100 days. 

Subcutaneous injection of rabbits with aluminum chloride daily for 28 days was associated with significant accumulation of aluminum in bone, followed in order by significantly increased aluminum concentrations in renal cortex, renal medulla, liver, testes, skeletal muscle, heart, brain white matter, hippocampus, and plasma (Du Val et al. 1986). Because the brain tissue of treated rabbits had the lowest aluminum concentrations of the tissues evaluated, the authors suggested that there was a partial blood-brain barrier to entry of aluminum. 

Melethil SK Mechanism of blood-brain transport of aluminum in rats University of Missouri Kansas National Institute of Environmental Health Sciences... 

Recent measurements of aluminum concentrations in human tissues for estimation of exposures are primarily limited to bone and brain tissues (Nieboer et al. 1995). Background levels of aluminum in bone are in the order of 1-3 g/g (ppm, dry weight). These authors also reported that background aluminum levels in brain tissues (primarily grey matter) of healthy individuals typically ranges from 1 to 3 g/g (ppm, dry weight) or <0.5 g/g (wet weight). 

Inductively coupled plasma-mass spectrometry (ICP-MS) is a powerful technique that uses an inductively coupled plasma as an ion source and a mass spectrometer as an ion analyzer. It can measure the presence of more than 75 elements in a single scan, and can achieve detection limits down to parts per trillion (ppt) levels for many elements—levels that are two or three orders of magnitude lower than those obtained by ICP-AES (Keeler 1991). It is more expensive than ICP-AES and requires more highly skilled technical operation. Aluminum levels in urine and saliva were detected down to 0.02 g/mL and in blood serum to 0.001 g/mL using ICP-MS (Ward 1989). Speciation studies have employed ICP-MS as a detector for aluminum in tissue fractions separated by size-exclusion chromatography (SEC) with detection limits of 0.04 g/g in femur, kidney and brain (Owen et al. 1994). 

Dedman DJ, Treffry A, Candy JM, et al. 1992. Iron and aluminum in relation to brain ferritin in normal individuals and Alzheimer s-disease and chronic renal-dialysis patients. Biochem J 287 509-514. 

Exley C. 1996. Aluminum in the brain and heart of the rainbow trout. J Fish Biol 48 706-713. 

Golub MS, Han B, Keen CL, et al. 1993a. Developmental patterns of aluminum in mouse brain and effects of dietary aluminum excess on manganese deficiency. Toxicology 81 33-47. 

Good PF, Olanow CW, Perl DP. 1992a. Neuromelanin-containing neurons of the substantia nigra accumulate iron and aluminum in Parkinson s disease A LAMMA study. Brain Res 593 343-346. 

Julka D, Vasishta RK, Gill KD. 1996. Distribution of aluminum in different brain regions and body organs of rat. Biol Trace Elem Res 52 181-192. 

Lovell MA, Ehmann WD, Markesbery WR. 1993. Laser microprobe analysis of brain aluminum in Alzheimer s disease. Ann Neurol 33 36-42. 

Markesbery WR, Ehmann WD, Hossain TIM, et al. 1981. Instrumental neutron activation analysis of brain aluminum in Alzheimer disease and aging. Ann Neurol 10 511-516. 

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