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International Journal of Alzheimer’s Disease
Volume 2012, Article ID 914947, 17 pages
http://dx.doi.org/10.1155/2012/914947
Review Article

Cognitive Deterioration and Associated Pathology Induced by Chronic Low-Level Aluminum Ingestion in a Translational Rat Model Provides an Explanation of Alzheimer's Disease, Tests for Susceptibility and Avenues for Treatment

1Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
2Clinical Outcomes Research, St George Hospital, Kogarah, NSW 2217, Australia

Received 15 January 2012; Accepted 17 May 2012

Academic Editor: Peter Rapp

Copyright © 2012 J. R. Walton. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

A translational aging rat model for chronic aluminum (Al) neurotoxicity mimics human Al exposure by ingesting Al, throughout middle age and old age, in equivalent amounts to those ingested by Americans from their food, water, and Al additives. Most rats that consumed Al in an amount equivalent to the high end of the human total dietary Al range developed severe cognitive deterioration in old age. High-stage Al accumulation occurred in the entorhinal cortical cells of origin for the perforant pathway and hippocampal CA1 cells, resulting in microtubule depletion and dendritic dieback. Analogous pathological change in humans leads to destruction of the perforant pathway and Alzheimer's disease dementia. The hippocampus is thereby isolated from neocortical input and output normally mediated by the entorhinal cortex. Additional evidence is presented that Al is involved in the formation of neurofibrillary tangles, amyloid plaques, granulovacuolar degeneration, and other pathological changes of Alzheimer’s disease (AD). The shared characteristics indicate that AD is a human form of chronic Al neurotoxicity. This translational animal model provides fresh strategies for the prevention, diagnosis, and treatment of AD.