Aluminium in the human brain

Abstract

An inevitable consequence of humans living in the Aluminium Age is the presence of aluminium in the brain. This non-essential, neurotoxic metal gains entry to the brain throughout all stages of human development, from the foetus through to old age. Human exposure to myriad forms of this ubiquitous and omnipresent metal makes its presence in the brain inevitable, while the structure and physiology of the brain makes it particularly susceptible to the accumulation of aluminium with age. In spite of aluminium's complete lack of biological essentiality, it actually participates avidly in brain biochemistry and substitutes for essential metals in critical biochemical processes. The degree to which such substitutions are disruptive and are manifested as biological effects will depend upon the biological availability of aluminium in any particular physical or chemical compartment, and will under all circumstances be exerting an energy load on the brain. In short, the brain must expend energy in its 'unconscious' response to an exposure to biologically available aluminium. There are many examples where 'biological effect' has resulted in aluminiuminduced neurotoxicity and most potently in conditions that have resulted in an aluminiumassociated encephalopathy. However, since aluminium is non-essential and not required by the brain, its biological availability will only rarely achieve such levels of acuity, and it is more pertinent to consider and investigate the brain's response to much lower though sustained levels of biologically reactive aluminium. This is the level of exposure that defines the putative role of aluminium in chronic neurodegenerative disease and, though thoroughly investigated in numerous animal models, the chronic toxicity of aluminium has yet to be addressed experimentally in humans. A feasible test of the 'aluminium hypothesis', whereby aluminium in the human brain is implicated in chronic neurodegenerative disease, would be to reduce the brain's aluminium load to the lowest possible level by noninvasive means. The simplest way that this aim can be fulfilled in a significant and relevant population is by facilitating the urinary excretion of aluminium through the regular drinking of a silicic acid-rich mineral water over an extended time period. This will lower the body and brain burden of aluminium, and by doing so will test whether brain aluminium contributes significantly to chronic neurodegenerative diseases such as Alzheimer's and Parkinson's.

Ferrous iron formation following the co-aggregation of ferric iron and the Alzheimer's disease peptide β-amyloid (1–42)

“…The addition of aluminium appears to impact the reductive capacity of Aβ by increasing its ability to reduce iron(III) in suspension. Aluminium is also not naturally found within human tissues [51], and therefore its removal from brain tissue may act to reduce Aβ neurotoxicity, while not impacting healthy brain functions. In summary, key insights into the relationship between Aβ and iron have been made that provide valuable insights into the role played by iron in AD pathology.…”

Aluminium in human brain tissue: how much is too much?

“…Living in the 'aluminium age' ensures that the myriad ways in which we are exposed to aluminium today will be even more numerous tomorrow. Aluminium in human brain tissue is the inevitable consequence of this burgeoning exposure [2]. However, what are the consequences of aluminium in human brain tissue?…”

What is the risk of aluminium as a neurotoxin?

“…While aluminium's neurotoxicity is incontrovertible, it is much more difficult to understand the risk that this neurotoxin poses to human health. Aluminium is neurotoxic because it possesses an extensive biochemical toolkit and because neurons are predisposed by their longevity toward its intracellular accumulation up to and beyond toxic thresholds [2]. Aluminium is neurotoxic as the establishment of toxicity thresholds can result in neuronal dysfunction, neurodegeneration and ultimately neuronal cell death through a continuum of disruptive events from classical apoptosis through to sudden and violent necrosis [3].…”

“…What is currently unknown is how our burgeoning exposure to aluminium in everyday life is contributing toward toxic thresholds in individuals and in populations. Aging is a major risk factor for neurodegenerative diseases and it is also a significant risk factor for establishing brain burdens of aluminium [2]. The latter are not expected to achieve levels responsible for overt toxicity, such as were found for dialysis encephalopathy [11], but do they approach or exceed those required for covert toxicity, including exacerbation of an ongoing disease state?…”