Journal
NEUROBIOLOGY OF AGING
Volume 33, Issue 8, Pages 1633-1641Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.03.005
Keywords
Alzheimer's disease; Hemochromatosis and Transferrin gene variants; Iron status; Liver distress
Categories
Funding
- Italian Health Department: Profilo Biologico e Genetico della Disfunzione dei Metalli Nella Malattia di Alzheimer e Nel 'Mild Cognitive Impairment [RF 2006 conv.58]
- Programma-Strategico [conv. PS39]
- Ricerca Corrente grants IRCCS, Brescia, Italy
- ERA-Net NEURON (JTC)
- AFaR Foundation-Osp. Fatebenefratelli
- AAMS e il gioco sicuro
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It is now accepted that transition metals, such as iron and copper, are involved in the pathogenesis of the Alzheimer's disease (AD) through their participation in toxic oxidative phenomena. In this context, hemochromatosis (Hfe) and transferrin (Tf) genes are of particular importance, since they play a key role in iron homeostasis. Also, signs of liver distress which accompany metal dysmetabolisms have been shown to be linked to AD. In order to investigate whether and how all these factors are interconnected, in this study we have explored the relationship of the gene variants of Hfe H63D and C282Y and of Tf C2 with serum markers of iron status (iron, ferritin, TF, TF-saturation, ceruloplasmin -CP-, CP and TF serum concentrations (CP/TF) ratio), and of liver function (albumin, transaminases, prothrombin time-prothrombin time (PT)) in a sample of 160 AD patients and 79 healthy elderly controls. Albumin resulted in lower, PT longer and AST/ALT higher ratios in AD patients than in controls, indicating a distress of the liver. Also TF was lower and ferritin higher in AD. Multiple logistic regression backward analyses, performed to evaluate the effects of our biochemical variables upon the probability of developing AD, revealed that a one-unit TF serum-decrease increases the probability of AD by 80%, a one-unit albumin serum-decrease reduces this probability by 20%, and a one-unit increase of AST/ALT ratio generates a 4-fold probability increase. Patients who were carriers of the H63D mutation showed higher levels of iron, lower levels of TF and CP and higher CP/TF ratios, a panel resembling hemochromatosis. This picture was found neither in H63D non-carrier patients, nor in healthy controls. Our results suggest the existence of a link between Hfe mutations and iron abnormalities that increases the probability of developing AD when accompanied by a distress of the liver. (C) 2012 Elsevier Inc. All rights reserved.
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