Affiliations: [a] Department of Pathology, University of Virginia, Charlottesville, VA, USA | [b] IRP, NIMH, NIH, Bethesda, MD, USA | [c] Department of Pharmacology, Physiology and Therapeutics, University of North Dakota School of Medicine, Grand Forks, ND, USA | Program of Cognitive Neuroscience, Department of Psychology, Babeş-Bolyai University, Cluj-Napoca, CJ, Romania
Correspondence:
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Corresponding author: John Savory, P.O. Box 800168, Department of Pathology, University of Virginia Health Sciences Center, Charlottesville, VA, USA. Tel.: +1 434 924 5682; Fax: +1 434 924 2574.
Note: [1] Supported by Grant R-82978201 from the Environmental Protection Agency.
Abstract: For four decades the controversial question concerning a possible role for aluminum neurotoxicity in contributing to the pathogenesis of Alzheimer's disease has been debated, and studies by different investigators have yielded contradictory results. The lack of sensitivity to aluminum neurotoxicity in transgenic mouse models of Alzheimer's disease has not allowed the system to be used to explore important aspects of this toxicity. Rabbits are particularly sensitive to aluminum neurotoxicity and they develop severe neurological changes that are dependent on dose, age and route of administration. The most prominent feature induced by aluminum in rabbit brain is a neurofibrillary degeneration that shares some similarity with the neurofibrillary tangles found in Alzheimer's disease patients. In the present review we discuss data from our laboratory and others, on the effects of aluminum on behaviour, neurologic function and morphology, using aluminum administered to rabbits via different routes. Finally, we will examine data on the possible cellular mechanisms underlying aluminum neurotoxicity, and potential neuroprotective strategies against aluminum toxicity.
