Association Between Serum Ceruloplasmin Specific Activity and Risk of Alzheimer's Disease

J Alzheimers Dis. 2016;50(4):1181-9. doi: 10.3233/JAD-150611.


Meta-analyses demonstrate copper involvement in Alzheimer's disease (AD), and the systemic ceruloplasmin status in relation to copper is an emerging issue. To deepen this matter, we evaluated levels of ceruloplasmin concentration, ceruloplasmin activity, ceruloplasmin specific activity (eCp/iCp), copper, non-ceruloplasmin copper iron, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype in a sample of 84 AD patients and 58 healthy volunteers. From the univariate logistic analyses we found that ceruloplasmin concentration, eCp/iCp, copper, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype were significantly associated with the probability of AD. In the multivariable logistic regression analysis, we selected the best subset of biological predictors by the forward stepwise procedure. The analysis showed a decrease of the risk of having AD for eCp/iCp (p = 0.001) and an increase of this risk for non-ceruloplasmin copper (p = 0.008), age (p = 0.001), and APOE-ɛ4 allele (p < 0.001). The estimated model showed a good power in discriminating AD patients from healthy controls (area under curve: 88% ; sensitivity: 66% ; specificity 93%). These data strength the breakdown of copper homeostasis and propose eCp/iCp as a reliable marker of ceruloplasmin status.

Keywords: Alzheimer’s disease; ceruloplasmin; ceruloplasmin specific activity; non-ceruloplasmin copper.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / blood*
  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / genetics
  • Apolipoprotein E4 / genetics
  • Area Under Curve
  • Biomarkers / blood
  • Blood Chemical Analysis
  • Ceruloplasmin / metabolism*
  • Copper / blood
  • Female
  • Genotype
  • Genotyping Techniques
  • Humans
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Prognosis
  • ROC Curve
  • Risk
  • Sensitivity and Specificity
  • Transferrin / metabolism


  • Apolipoprotein E4
  • Biomarkers
  • Transferrin
  • Copper
  • Ceruloplasmin