Affiliations: [a] Department of Neuroscience & Anatomy, Penn State University College of Medicine, M.S. Hershey Medical Center, Hershey PA, USA | [b] Department of Neurology, Johns Hopkins University, Baltimore MD, USA | [c] Department of Physiology, University of Toronto, Toronto ON, Canada | [d] Department of Internal Medicine, University of Milan & IRCCS Ospedale Maggiore, Milan, Italy | [e] Department of Pathology, Penn State University College of Medicine, M.S. Hershey Medical Center, Hershey PA, USA | [f] Department of Microbiology & Immunology, Penn State University College of Medicine, M.S. Hershey Medical Center, Hershey PA, USA | [g] Discipline of Medical Genetics, Faculty of Medicine and Health Sciences, University of Newcastle, Australia
Correspondence:
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Corresponding author.
Note: [] Communicated by Paolo Zatta.
Abstract: Excess iron accumulation in the brain is a consistent observation in Alzheimer's Disease. Iron affects amyloid precursor protein (AβPP) processing and promotes deposition of Aβ. Iron is also among the most potent biological toxins because of its ability to react with oxygen to form reactive oxygen species. Consequently, elucidation of the mechanisms associated with maintaining brain iron homeostasis is fundamentally important to understanding the underlying pathogenesis in AD. The iron overload disorder, Hemochromatosis, is the most common genetic disorder (1:200) so a significant percentage of AD patients can be expected to carry this mutation. Heterozygotes for this mutation also have an increased, but sub-clinical iron burden. Given the high percentage of the population who are at significant risk for iron overload, we propose that the hemochromatosis mutation be considered as a confounding factor when evaluating the contribution of genetic associations with AD and treatment strategies and efficacy. Two recent papers and new evidence presented here that the protein associated with hemochromatosis is expressed on blood vessels, choroid plexus and the ependymal cells in the brain are offered as support for this proposal.
