Preface: Why is Research into Aluminium and Life Important?

Christopher Exleycha38@keele.ac.uk, Birchall Centre for Inorganic Chemistry and Materials Science, School of Chemistry and Physics, Keele University, Keele, Staffordshire, ST5 5BG, UK

Summary

The versatility of aluminium chemistry will ensure its burgeoning use in the future in all manner of applications. This very same chemistry will also ensure its increased biological availability in all biota including Man. We do not know enough about the biological chemistry of a chronic exposure to aluminium to be able to predict its impact on human health. The scientific evidence linking aluminium with Alzheimer’s disease is as strong as it is for any other single aetiological agent. If we can identify where aluminium fits into the aetiology or pathogenesis of diseases such as Alzheimer’s we may be able to accurately assess the risk to human health posed by biologically available aluminium.

Personal Perspective

The natural abundance of aluminium (Al) and the development at the end of the nineteenth century of its electrolytic refinement have conspired to make Al the most widely used and diversely applied metal of our age. Behind many of its successful applications is an extremely versatile chemistry which will lend itself to the continued and varied use of Al in the future (Atwood & Yearwood, 2000). Man-made alterations in the environment, such as the acidification of land by, for example, the impact of acidic deposition or the extensive use of intensive agriculture, and Man’s use of Al in everyday life are increasing its abundance in the biosphere relative to the lithosphere and, concomitantly, its biological availability or potential to participate in the processes of life and, ultimately, evolution (Exley & Birchall, 1992). Therefore, it is important that we understand the biological chemistry of Al and, in particular, in its relation to human health.

The widespread use of products made from or containing Al is ensuring the omnipresence of Al in our bodies. It is unlikely that Al is absent from any organ, tissue, body fluid or even cell in our body. New research continues to document our burgeoning exposure to Al (for example, Linebarger et al., 1999; Roider & Drasch, 1999; Mora et al., 1999; Kristjansson et al., 2000; Dawson et al., 2000; Schlesinger et al., 2000) and, in some cases, has linked the observed burden of Al to human health (for example, Hovatta et al., 1998; Burge et al., 2000; Riihimäki et al., 2000; Shanklin et al., 2000). Every year new research highlights aspects of the biological chemistry of Al which might help to explain much of its known toxicity (for recent examples see; Toninello et al., 2000; Vieira et al., 2000; Jankowska et al., 2000; González-Revaldería et al., 2000; Berg et al., 2000; Verstraeten & Oteiza, 2000; Tanino et al., 2000; Zatta et al., 2000; Zatta et al., 2000; Struys-Ponsar et al., 2000; Lévesque et al., 2000; Smans et al., 2000; Hong et al., 2000; Mahieu et al., 2000). However, the emergence of Al as an environmental toxin has not yet received serious recognition in human toxicology. It is intriguing that the advent of the recognition that the most abundant metal in the lithosphere is inimical to life has not been sufficient by itself to arouse the precautionary principle in the same way as has recently been the case in Europe with, for example, transmissible encephalopathies? It is clear that many equate the omnipresence of Al with a benign influence on health. It is reasoned that Al toxicity can only be as the result of an acute exposure to the metal and that an event of this kind will be extremely rare in the general population. It is true that Man’s systemic absorption of Al is limited and that this will reduce the likelihood of an acute exposure. However, it is a coincidence of Al chemistry that the systemic absorption of Al is low. There is no evidence that the exclusion of Al from the body is the result of evolutionary pressure. Likewise there is not an element specific reaction to the presence of systemic Al. There is no homeostatic control of the concentration of Al in either the intracellular or the extracellular environment. Al is a silent visitor to our bodies and its transport and fate are governed by a large number of Trojan Horse-like molecules. We are fortunate that some of these molecules facilitate the removal of Al from the body via the kidney. However, other molecules actually contribute towards an increase in the body burden of Al by delivering it to more permanent body stores such as bone and, the brain.

The brain is an obvious target for chronic Al intoxication. The longevity of neurones identifies them as sinks for systemic Al. The uptake of Al into the brain is at least an order of magnitude more efficient than its release (Yokel et al., 2000) and this ensures an increase in neuronal Al with age. There can be no dispute over the presence, and indeed accumulation, of Al in the human brain. The task now is to identify the biological chemistry of the brain Al burden and how it may be influenced by brain biochemistry and physiology in health and disease.

The research summarised in this book in concert with the informed opinions of the authors have provided the most up to date account of the science that describes the link between Al and Alzheimer’s disease (AD). The subject has been reviewed from the perspective of delineating what we think we know about Al (Historical Perspective), including exposure, human disease, animal models of disease, toxicokinetics and cell biochemistry, and then using this information to think about what we do not know about Al and AD (Informed Opinion). Certainly Al is not inert in the body. Wherever it is found it will be biologically available. The question is whether the biological reactivity of Al is sufficient to influence essential biochemical processes or physiological functions in any particular environment. In the brain, during an acute exposure to Al, for example, as has occurred in dialysis encephalopathy, the concentration of biologically available Al will be both high and persistent and normally robust biochemistry will be irreversibly altered within a very short timeframe. However, when the brain is subjected to a chronic exposure to Al (similar, perhaps, to our everyday exposure to the metal) the concentration of biologically available Al in the brain will be low, though it will increase with age and it will persist throughout the lifetime of the individual. The ability of the brain to cope with this persistent challenge will reflect individual differences in brain physiology and brain uptake and accumulation of Al. It will be this balance which will dictate whether or not Al will influence brain function and not simply the brain burden of the metal. In AD there is a selective and progressive loss of cognitive function which precedes neuronal loss and the formation of characteristic pathology. Al has been implicated in each stage of the disease and it is only a red mist of controversy and not any decision based upon sound scientific principles that has blinded some individuals and organisations to its possible role in the aetiology of the disease. We have not been able to conclude a specific role for Al in AD. However, neither have we concluded that Al is a benign influence in the disease. We hope that this book will act as a stimulus to much needed further research into the biological chemistry of Al and the link between Al and AD.