Effects of hemochromatosis and transferrin gene mutations on iron dyshomeostasis, liver dysfunction and on the risk of Alzheimer's disease

Federica Giambattistelli, Serena Bucossi, Carlo Salustri, Valentina Panetta, Stefania Mariani, Mariacristina Siotto, Mariacarla Ventriglia, Fabrizio Vernieri, Maria Luisa Dell'Acqua, Emanuele Cassetta, Paolo Maria Rossini, Rosanna Squitti

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1633-1641
Number of pages9
JournalNeurobiology of Aging
Issue number8
Publication statusPublished - Aug 2012


  • Alzheimer's disease
  • Hemochromatosis and Transferrin gene variants
  • Iron status
  • Liver distress

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology


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