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International Journal of Alzheimer’s Disease
Volume 2011 (2011), Article ID 276393, 17 pages
Review Article

Link between Aluminum and the Pathogenesis of Alzheimer's Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses

1Department of Analytical Chemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino-cho, Nobeoka-shi, Miyazaki 882-8508, Japan
2Institute of Industrial Science (IIS), The University of Tokyo, 4-6-1 Komaba, Meguro-ku, Tokyo 153-8904, Japan

Received 15 September 2010; Revised 29 November 2010; Accepted 5 January 2011

Academic Editor: Paolo Zatta

Copyright © 2011 Masahiro Kawahara and Midori Kato-Negishi. 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.


Whilst being environmentally abundant, aluminum is not essential for life. On the contrary, aluminum is a widely recognized neurotoxin that inhibits more than 200 biologically important functions and causes various adverse effects in plants, animals, and humans. The relationship between aluminum exposure and neurodegenerative diseases, including dialysis encephalopathy, amyotrophic lateral sclerosis and Parkinsonism dementia in the Kii Peninsula and Guam, and Alzheimer's disease (AD) has been suggested. In particular, the link between aluminum and Alzheimer's disease has been the subject of scientific debate for several decades. However, the complex characteristics of aluminum bioavailability make it difficult to evaluate its toxicity and therefore, the relationship remains to be established. Mounting evidence has suggested that significance of oligomerization of -amyloid protein and neurotoxicity in the molecular mechanism of AD pathogenesis. Aluminum may play crucial roles as a cross-linker in -amyloid oligomerization. Here, we review the detailed characteristics of aluminum neurotoxicity based on our own studies and the recent literatures. Our aim is to revisit the link between aluminum and AD and to integrate aluminum and amyloid cascade hypotheses in the context of -amyloid oligomerization and the interactions with other metals.