Aluminosilicates and Senile Plaque Formation in Alzheimer's Disease

Candy, J.; Klinowski, Jacek; Perry, Robert H.; Perry, Elaine K.; Fairbairn, Andrew; Oakley, Arthur E.; Carpenter, T. A.; Atack, John; Blessed, G.; Edwardson, J. A.

doi:10.1016/s0140-6736(86)92319-6

Cited by 456 publications

(107 citation statements)

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“…Abnormal accumulation of aluminium has also been detected within the brain tissue of patients with Alzheimer's disease and the Parkinsonian dementia complex of Guam Perl et al, 1982;Candy et al, 1986). Aluminium salts also induce memory impairment in susceptible experimental animals, accompanied by the formation of neuronal cytoskeletal abnormalities (Klatzo et al, 1965;.…”

Section: Introductionmentioning

confidence: 99%

Effects of aluminium on electrical and mechanical properties of frog atrial muscle

Meiri

Shimoni

1991

British J Pharmacology

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The effects of aluminium on membrane ionic currents were studied in single cardiac myocytes. Most of the work was done on frog atrial cells, but some experiments were also carried out on single cells isolated from rabbit ventricles and atria. The effects of aluminium on the force of contraction of frog atrial trabeculae were also investigated. Aluminium was prepared from AlCl3 as a stock 0.5 m solution which has a pH of 3.5. Before each experiment, this solution was added to the control solution, to give a final concentration of 20–100 μg ml−1 aluminium (0.75–3.75 mm AlCl3). The solutions were brought to a pH of 7.4 or 7.6, at which they consist of a mixture of amorphous aluminium hydroxides and a very small amount of soluble ionic aluminium complexes: free aluminium cations (less than 10 pm), aluminohydroxide anions (less than 8 μm). The addition of this suspension reduced the peak inward calcium currents in single rabbit atrial and ventricular cells and in frog atrial cells. In the latter, the peak current was reduced (at + 10 mV) to 45% of control (mean of 9 cells). This effect was reversible upon washout, and was obtained at all membrane potentials, with no shift of the calcium current voltage relationship along the voltage axis. Aluminium also reduced the time‐dependent potassium current IK. This reduction was observed at all membrane potentials. For example, at + 10 mV, the mean reduction of IK (n = 9) was to 69% of the control amplitude. This effect, which was very difficult to reverse, was not due to IK rundown. The fully activated current‐voltage relationships (obtained by standard ‘tail’ analysis) showed that the effect of aluminium was due mainly to a decrease in conductance and not to a shift in the activation range of IK. The mean voltage of half activation was shifted by 8 mV in the depolarizing direction (n = 5). The background potassium current IK1 was also slightly but consistently changed in a complex fashion, with an outward shift at membrane potentials positive to −60 mV. For example, at a membrane potential of −40 mV, the mean shift was by 22 ± 4 pA. At more negative potentials, there was an inward shift in the current amplitudes. For example, for steps to −100 mV the current elicited was larger (more inward) by 53 pA (mean value, n = 10). The reversal potential was slightly shifted (< 10 mV) in the hyperpolarizing direction. The force of contraction of frog atrial trabeculae was altered by aluminium in a complex manner, which showed marked seasonal variation. During most of the year, 50–100 μg ml−1 aluminium caused a biphasic change, with an early small and consistent decrease, followed by a large increase in twitch amplitude. For a short period corresponding to the (local) winter months the sensitivity to aluminium was greatly enhanced. Aluminium 100 μg ml−1 totally abolished contraction (n = 5), while a lower concentration (20 μg ml−1) produced a sustained reduction in the force of contraction. Similar biphasic and seasonal responses have been reported to be induced by lanthanum. The biph...

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Section: Introductionmentioning

confidence: 99%

Effects of aluminium on electrical and mechanical properties of frog atrial muscle

Meiri

Shimoni

1991

British J Pharmacology

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“…Tangles contain abnormally phosphorylated tau protein that combine to form paired helical filaments within the neuron (5). In addition to the protein components of plaques and tangles, some researchers have detected aluminum (6, 7) and aluminosilicates (8) in these lesions, although the evidence for their presence is apparently controversial (9).…”

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confidence: 99%

Solubilization of beta-amyloid-(1-42)-peptide: reversing the beta-sheet conformation induced by aluminum with silicates.

Fasman

Perczel

Moore

1995

Proc. Natl. Acad. Sci. U.S.A.

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Plaques are one of the two lesions found in the brain of patients with Alzheimer disease. Using a synthetic peptide corresponding to rat ,B-amyloid-(1-42) (j3A4), circular dichroism (CD) analyses were performed to examine the effect of Na4SiO4 on the conformational state produced by Al3+. A previous study on fragments of neuronal proteins involved in tangle formation had shown a conformational transition from a 8-pleated sheet to a soluble random coil upon addition of Na4SiO4. In the present study, CD measurements showed that the f3-pleated sheet conformation of f3A4 induced by Al3+ was reversed to the random coil soluble form by the addition of Na4SiO4. The tight binding of Al3+ provides the mechanism for this transition. These results provide insight into the role of aluminum in the Alzheimer diseased brain and suggests the investigation of the use of silicates as a therapeutic agent.Alzheimer disease (AD) will probably become the predominant social-medical-economic problem in the next century. An estimated 4 million Americans now have the disease, and this number is expected to grow to >10 million within the next decade (1). The cause of AD is not known, and treatments are only mildly effective at slowing the degeneration process (2). The signs of AD, obtained upon autopsy of the diseased brain, reveal two phenomena: amyloid plaques and neurofibrillary tangles (3). The amyloid plaques are composed primarily of a 39-to 42-amino acid fragment (13A4) from the amyloid precursor protein (4). Tangles contain abnormally phosphorylated tau protein that combine to form paired helical filaments within the neuron (5). In addition to the protein components of plaques and tangles, some researchers have detected aluminum (6, 7) and aluminosilicates (8) in these lesions, although the evidence for their presence is apparently controversial (9).Aluminum is known to have toxic effects (10) on many organisms, including man. Aluminum is an associated risk factor in amyotrophic lateral sclerosis, Parkinsonismdementia of Guam, and AD (11,12).Aluminum is the third most abundant element in the earth's crust, found primarily as insoluble aluminosilicates and oxides. However, it is soluble as aluminum hydroxide and aluminum hydrates at acidic pH values (13). This has become a biologic concern as the world's water supplies become more acidic due to acid rain. For (18,19). The formation of 13-pleated sheets could be reversed by the addition of silicates (20).The current paper is a study of the ,3A4 peptide (residues 1-42 of the ,B-amyloid precursor protein), whose prominent role in the progression of AD has been frequently stressed and has been reviewed extensively (21-23). Several structural studies on 13A4 or its fragments have been reported (24)(25)(26)(27)(28). CD studies illustrated the requirements for 13-sheet filament formation (29). Solid-state Fourier-transform infrared spectroscopy showed that the secondary structure consisted of a 13-turn flanked by two strands of antiparallel 1-pleated sheet (30). In aqueous tri...

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“…There is also an epidemiological association between aluminium in drinking water and the incidence of Alzheimer's disease (Martyn et al, 1989). Histological analysis have also revealed high concentration of aluminium in the nuclei of neurones associated with neurofibrillary tangle in Alzheimer's disease, and senile plaques (Candy et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

The effects of aluminium and selenium supplementation on brain and liver antioxidant status in the rat

Abubakar¹,

Taylor²,

Ferns³

2004

Afr. J. Biotechnol.

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This in vivo study was designed to investigate the potential of aluminium (Al), in the absence of added iron, to participate in either antioxidant or pro-oxidant events. Some markers of oxidative stress were determined in liver and brain of rats exposed to aluminium lactate, either alone or in the presence of dietary supplements of selenium (se) as selenite. Exposure to aluminium for 21 days resulted in a statistically significant (P<0.05) decrease in brain glutathione. However, a non-significant increase in hepatic glutathione was observed in animals supplemented with either Se or Al, but Al in combination with Se prevented this elevation. In the brain a statistically non-significant increase (P>0.05) was observed in the GSH content. Contrary to what is known, Al exposure resulted in statistically significant decrease (P<0.001) in lipid peroxidation as measured by production of malondialdehyde in both liver and brain. Aluminium exposure had no significant effect on the liver and brain superoxide dismutase activity. Results of the present study suggest that in rat aluminium exposure may have both pro-oxidant and antioxidant effect. Furthermore, Se supplementation may offer some protection against aluminium toxicity but this needs to be further elucidated.

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Aluminosilicates and Senile Plaque Formation in Alzheimer's Disease

Cited by 456 publications

References 9 publications

Effects of aluminium on electrical and mechanical properties of frog atrial muscle

Effects of aluminium on electrical and mechanical properties of frog atrial muscle

Solubilization of beta-amyloid-(1-42)-peptide: reversing the beta-sheet conformation induced by aluminum with silicates.

The effects of aluminium and selenium supplementation on brain and liver antioxidant status in the rat

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