Metal-score as a potential non-invasive diagnostic test for Alzheimer's disease

Paolo Maria Rossini, Rosanna Squitti, Patrizio Pasqualetti, Renato Polimanti, Carlo Salustri, Filomena Moffa, Emanuele Cassetta, Domenico Lupoi, Mariacarla Ventriglia, Maurizio Cortesi, Mariacristina Siotto, Fabrizio Vernieri

Research output: Contribution to journalArticle

24 Citations (Scopus)


The link between biometals and Alzheimer's disease (AD) has been investigated with a focus on local metal accumulations. In this work, we have looked at systemic metal changes and computed a score (M-score) based on metal disarrangements to discriminate patients with AD from patients with vascular dementia (VaD) and from controls. We measured serum levels of iron, copper, ceruloplasmin, transferrin, and total antioxidant capacity (TAS), performed Apolipoprotein E (APOE) genotyping and calculated non-ceruloplasmin copper ('free' copper') levels, transferrin saturation, total iron binding capacity, and ceruloplasmin-transferrin ratio (Cp/Tf) in 93 patients with AD, 45 patients with VaD, and 48 controls. All subjects underwent biochemical, neuroimaging and cognitive evaluations. Significant differences were observed among the tested groups for the levels of copper, free copper, peroxides, and TAS and for the Cp/Tf with disparity in couple comparison. On this basis we created the M-score as linear combination of biometal variables and APOE genotype. Besides its ability to discriminate AD patients vs. controls (ROC AUC=90%), M-score was able to distinguish AD vs. VaD (ROC AUC=79%). Moreover, we calculated the sensitivity and the specificity for M-score and for the other significant variables: M-score reached the highest sensitivity without a relevant loss in terms of specificity. When we compared M-score with APOE genotype and Medial Temporal Atrophy score, it resulted statistically better than these diagnostic markers. In conclusion, we confirm the link between biometals and AD and suggest its potential as diagnostic tool. Further studies may elucidate its potential role as reliable diagnostic test.
Original languageEnglish
Pages (from-to)191-198
Number of pages8
JournalCurrent Alzheimer Research
Publication statusPublished - 2013


  • Aged
  • Aged, 80 and over
  • Alzheimer Disease
  • Analysis of Variance
  • Antioxidants
  • Apolipoprotein E4
  • Ceruloplasmin
  • Copper
  • Dementia, Vascular
  • Female
  • Humans
  • Iron
  • Male
  • Metals
  • Middle Aged
  • ROC Curve
  • Transferrin


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