Aluminosilicate-lnduced Free Radical Generation by Murine Brain Glial Cells in vitro: Potential Significance in the Aetiopathogenesis of Alzheimer's Dementia

Abstract

While previous studies have identified aluminosilicate deposits within the senile plaque cores from subjects with Alzheimer''s dementia, their possible role in the aetiopathogenesis of the disease remains unknown. In the present in vitro chemiluminescent study, we show that cultured murine glial cells exhibit the capacity to generate free radical and related oxygen-derived metabolites when exposed to various natural and synthetic model aluminosilicate particulate samples of differing particle size, morphology and composition. These results, if applicable to the proposed analogous in vivo situation in humans, suggest that further research into the biochemical and cellular mechanisms influencing the production and modulation of tissue-injurious free radical oxygen-derived metabolites within the brain, could have significant implications in the pathogenesis, prevention and treatment of Alzheimer''s disease.

The promotion of iron-induced generation of reactive oxygen species in nerve tissue by aluminum

“…Thus, the presence of a membrane fraction is needed for the potentiation described. A proposal has been made that aluminum-silicon complexes, such as zeolite or kaolin, may be the most potent accelerators of iron-based oxidative stress (Carrel et al, 1994) and that these may be related to the pathogenesis of Alzheimer disease (Evans et al, 1992). The formation of ROS within the cortical P2 fraction was inhibited by a colloidal suspension of kaolin at a concentration of 170 µg/mL.…”

The relationship between excitotoxicity and oxidative stress in the central nervous system

“…73 Aluminosilicate deposits are known to be present within senile plaque cores, and this material has recently been shown to induce ROS generation. 82 The presence of ferritin in the senile plaque, has also been proposed as evidence for a role for free radicals in amyloid formation. 83 There is less evidence for a relation between AD and chronic low level hyperexcitatory events.…”

Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration

“…Despite the chemical inertness of its salts, there are many potential mechanisms by which Al can promote neurotoxic events (Tomljenovic, 2011). The induction of glial activation and initiation of macrophage responsivity by Al complexes has been frequently described many times (Evans et al, 1992;Gorell et al, 1999;Platt et al, 2001) but the means by which Al salts promote inflammatory events are unclear. Aluminum salts can provoke inflammatory glial responses in isolated systems as well as in intact animals, and so it is likely that they can act directly upon responsive glial cells (Campbell et al, 2002).…”