Affiliations: [a] 12 Sir Francis Wyatt Place, Newport News, VA 23606-3660, USA. E-mail: wbgrant@infi.net | [b] Department of Community & Environmental Medicine, University of California, Irvine, CA, 92697-1820, USA. E-mail: aghadimi@uci.edu | [c] Molecular Neurobiology Laboratory, Department of Optometry and Neuroscience, UMIST, Manchester M60 1QD, UK. E-mail: ruth.itzhaki@umist.ac.uk | [d] Departments of Pathology, Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, 22908, USA. E-mail: js2r@virginia.edu
Abstract: The proposition that environmental agents, such as diet, aluminum, and viruses, are as important as genetic factors in the etiology of Alzheimer's disease (AD) was advanced by the authors at the Challenging Views of Alzheimer's Disease meeting held in Cincinnati on July 28 and 29, 2001. Diet, dietary fat, and to a lesser extent, total energy (caloric intake), were found to be significant risk factors for the development of AD in a dozen countries, while fish consumption was found to be a significant risk reduction factor. An acid-forming diet, such as one high in dietary fat or total energy, can lead to increased serum and brain concentrations of aluminum and transition metal ions, which are implicated in oxidative stress potentially leading to the neurological damage characteristic of AD. Many of the risk factors for AD, such as cholesterol and fat, and risk reduction factors, such as whole grain cereals and vegetables, are shared with ischemic heart disease. Aluminum may cause neurological damage and a number of studies have linked aluminum to an increased risk for developing AD. The evidence for viral agents playing a role in AD is the strong association between the presence of HSV1 in brain and carriage of an apoE-ε4 allele in the case of AD patients but not of controls; statistical analysis shows the association is causal. Diet, aluminum, and viral infections may increase the prevalence of AD by eliciting inflammation, which may cause the neurological damage that results in AD.
