Elevated iron and zinc in alzheimer hippocampus

Abstract

Background: Iron and zinc are essential for the normal brain physiology. However an imbalance of these metals has been postulated to play a role in the pathogenesis of AD. We aimed to correlate levels of iron and zinc with the cognitive status and beta amyloid burden in postmortem well-characterized cases. Methods: Subjects with AD (n ¼ 13) and normal cognition (n ¼ 19) of the Brain Brain of Brazilian Aging Brain Study Group were classified according to the clinical and neuropathological evaluations. The clinical diagnosis was established through a postmortem interview with an informant including validated scales and questionnaries The neuropathological examinations were carried out based on accepted criteria, using immunohistochemistry. Neuropathologically, AD was defined by a CERAD 3 B and a Braak and Braak 3 IV. Levels of Fe and Zn were measured in the hippocampus using instrumental neutron activation analysis (INAA). Certified reference materials were analysed for assuring the quality of the analitycal results. Protocols were approved by the local ethics committee. The statistical analysis was performed using the IBM PAWS Statistics Package v.18 and Minitab Statistical Software v.15. Results: Significantly higher (p < 0.05) concentrations for Fe and Zn were found in the hippocampus of AD cases. The level of these elements was correlated to the amyloid plaques burden. Conclusions: Brain iron and zinc accumulation are a prominent feature of advanced Alzheimer disease. Recent evidence suggests that beta amyloid precipitation and toxicity by formation of H2O2 and increase of oxidative stress in AD are caused by abnormal interactions with metal ions, especially Zn and Fe. Our findings corroborate this hypothesis. However the exactly role of the iron and zinc alterations in brain in the pathogenesis of AD is yet to be clarifyed.