Link between Aluminum and the Pathogenesis of Alzheimer′s Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses

Abstract

Whilst being environmentally abundant, aluminum is not essential for life. On the contrary, aluminum is a widely recognized neurotoxin that inhibits more than 200 biologically important functions and causes various adverse effects in plants, animals, and humans. The relationship between aluminum exposure and neurodegenerative diseases, including dialysis encephalopathy, amyotrophic lateral sclerosis and Parkinsonism dementia in the Kii Peninsula and Guam, and Alzheimer's disease (AD) has been suggested. In particular, the link between aluminum and Alzheimer's disease has been the subject of scientific debate for several decades. However, the complex characteristics of aluminum bioavailability make it difficult to evaluate its toxicity and therefore, the relationship remains to be established. Mounting evidence has suggested that significance of oligomerization of β-amyloid protein and neurotoxicity in the molecular mechanism of AD pathogenesis. Aluminum may play crucial roles as a cross-linker in β-amyloid oligomerization. Here, we review the detailed characteristics of aluminum neurotoxicity based on our own studies and the recent literatures. Our aim is to revisit the link between aluminum and AD and to integrate aluminum and amyloid cascade hypotheses in the context of β-amyloid oligomerization and the interactions with other metals.

Aluminium chloride promotes anchorage‐independent growth in human mammary epithelial cells

“…Based on this observation, on the large array of effects by which aluminium has been reported to affect cellular physiology, including genotoxicity (Kawahara and Kato-Negishi, 2011;Banasik et al, 2005;Lankoff et al, 2006), on its wellestablished neurotoxic profile (Kawahara and Kato-Negishi, 2011;Krewski et al, 2007), and on its high concentration in antiperspirants, it has been hypothesized that aluminium might play a causal role in the carcinogenesis of the human mammary epithelium (Darbre, 2003(Darbre, , 2005. However, very little or no experimental data supporting this hypothesis exist.…”

“…In the latter cell type, this effect correlated with the induction of apoptosis (Banasik et al, 2005;Lankoff et al, 2006). Although the molecular basis of the genotoxic effect of aluminium has not been defined, it has been hypothesized to be mediated by direct interaction of aluminium with DNA, by the induction of oxidative DNA damage, by the release of lysosomal DNase, or by interference with normal microtubule function or with cellular DNA repair mechanisms (Banasik et al, 2005;Lankoff et al, 2006;Kawahara and Kato-Negishi, 2011). As discussed above, the effect of aluminium on human mammary epithelial cells reported in this study seems to be mediated in part by proliferation stress.…”

“…Overall, little is known about its toxic effects at the cellular and systemic levels, although it is generally acknowledged that aluminium is neurotoxic (Krewski et al, 2007;Kawahara and Kato-Negishi, 2011). With respect to the breast, relatively high levels of aluminium have been measured in the normal human breast adjacent to breast tumours (Exley et al, 2007), in the nipple aspirate fluid collected from women affected by breast cancer (Mannello et al, 2011), and in the fluid collected from breast cysts observed in gross cystic breast disease (Mannello et al, 2009), a benign breast disorder believed to facilitate the appearance of breast cancer.…”

Utilizing Magnesium based Materials to Reduce Green House Gas Emissions in Aerospace Sector

“…On the contrary, aluminum is neurotoxic and its use must be minimized. Intake of aluminum may lead to cognitive deficiency, dementia, adverse effect on central nervous system and reproductive system [17,18]. Accordingly, the recycling of aluminum will need technological efforts and its presence in food chain will only be detrimental to living organisms.…”

Disruption of Calcium Homeostasis in Alzheimer’s Disease: Role of Channel Formation by β Amyloid Protein

“…Substances that can influence the oligomerization processes, e.g., cholesterol or its oxidation products, transthyretin, rifampicin, curcumin, aspirin, docosahexaenoic acid (DHA) and peptides such as the β-sheet breaker peptide, reportedly inhibit AβP oligomerization in vitro. Among these factors, Al is of particular interest considering its epidemiological link with AD (Kawahara and Kato-Negishi, 2011). Al 3+ has strong positive charges and a relatively small ionic radius in comparison to other metal ions; thus, Al 3+ firmly binds to metalbinding amino acids (e.g.…”