Aluminum neurotoxicity

Patients with dialysis dementia respond positively to an antibody against the hyperphosphorylated microtubule-associated protein, tau, that accumulates in AD tangles (Guy et al. 1991). The neurofilament protein tubulin contains an acidic tau binding site to which Al might bind to cause tau accumulation. However, not only do dialysis dementia patients characteristically show no tangle formation, but the tangles seen in animals treated with Al are predominantly made up of neurofilament subunits such as tubulin, rather than microtubule-associated protein. A potential role for Al in G-protein-regulated neurofilament polymerization is discussed in Sect. G. 

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Numerous mechanistic studies of aluminum neurotoxicity have been performed, but the main sites of action have not been discerned as discussed in Section 2.4.2 and by Strong et al. (1996). Additional studies could help identify a single unifying mechanism that can explain and reconcile the wide variety of pathological, neurochemical, and behavioral effects of aluminum induced by oral exposure and in various model systems (e.g., intracerebral and intracistemal administration), but these kinds of studies are unlikely to better characterize neurotoxicity NOAELs and LOAELs relevant to MRL assessment. The relationship between aluminum exposure and neurotoxicity is an active area of research. 

Bishop NJ, Morley R, Day JP, et al. 1997. Aluminum neurotoxicity in preterm infants receiving intravenous-feeding solutions. N Engl J Med 336 1557-1561. 

Crapper-McLachlan DR. 1989. Aluminum neurotoxicity Criteria for assigning a role in Alzheimer s disease. In Lewis TE, ed. Environmental chemistry and toxicology of aluminum. Chelsea, MI Lewis Publishers, Inc., 299-315. 

Erasmus RT, Savory J, Wills MR, et al. 1993. Aluminum neurotoxicity in experimental animals. Ther Drug Monit 15 588-592. 

Gaytan-Garcia S, Kim H, Strong MJ. 1996. Spinal motor neuron neuroaxonal spheroids in chronic aluminum neurotoxicity contain phosphate-resistant high molecular weight neurofilament (NFH). Toxicology 108 17-24. 

Julka D, Gill KD. 1995. Development of a possible peripheral marker for aluminum neurotoxicity. Med SciRes 23 311-314. 

Kihira T, Yoshida S, Uebayashi Y, et al. 1994. Experimental model of motor neuron disease Oral aluminum neurotoxicity. BiomedRes 15 27-36. 

Kuroda Y, Kobayashi K, Ichikawa M, et al. 1995. Application of long-term cultured neurons in aging and neurological research Aluminum neurotoxicity, synaptic degeneration and Alzheimer s disease. Gerontology 41 (Suppl. l) 2-6. 

Shea TB. 1995. Calcium modulates aluminum neurotoxicity and interaction with neurofilaments. Mol Chem Neuropathol 24 151-163. 

Strong MJ, Garruto RM, Joshi JG, et al. 1996. Can the mechanisms of aluminum neurotoxicity be integrated into a unified scheme J Toxicol Environ Health 48 599-613. 

Bishop NJ, Robinson MJ, Lendon M, et al Increased concentration of aluminium in the brain of a parenterally fed preterm infant. Arch Dis Child 64 1316-1317, 1989 Bishop NJ, Morley R, Day JP, et al Aluminum neurotoxicity in preterm infants receiving intravenous-feeding solutions. N Engl J Med 336 1557-1561, 1997... 

SzuTOWicz A (2002) Aluminum Neurotoxicity. In Massaro EJ, ed. Handbook of Neurotoxicology pp. 211—236. Humana Press Inc, Totowa, NJ. 

Mechanisms of Aluminum Neurotoxicity— Relevance to Human Disease... 

Liss, L. (ed) (1980) Aluminum Neurotoxicity, Pathotox, Park Forest South, Illinois. 

Little information was available on aluminum neurotoxicity prior to the 1960s. Interest in aluminum has increased recently, particularly with the possibility of its involvement in the human diseases, Alzheimer s disease, and dialysis dementia (discussed below). 

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