Non-ceruloplasmin copper distinguishes a distinct subtype of alzheimer’s disease: A study of eeg-derived brain activity

Franca Tecchio, Fabrizio Vecchio, Mariacarla Ventriglia, Camillo Porcaro, Francesca Miraglia, Mariacristina Siotto, Paolo Maria Rossini, Mauro Rongioletti, Rosanna Squitti

Research output: Contribution to journalArticlepeer-review


Background: Meta-analyses show that percentages of non-Cp-Cu-copper that is not bound to ceruloplasmin (also known as ‘free’ copper)-in serum are higher in Alzheimer’s disease (AD) patients. Genetic heterogeneity in AD patients stratified on the basis of non-Cp-Cu cut-off sustains the existence of a copper AD metabolic subtype. Non-Cp-Cu abnormalities correlated with alterations of electroencephalographic rhythms (EEG). Objective: We aimed to determine whether an EEG-derived brain cortical rhythm’s heterogeneity between two AD groups stratified on the basis of a copper marker. Method: We assessed levels of copper, ceruloplasmin, Non-Cp-Cu, and the APOE4 genotype in 67 AD patients and compared resting EEG-derived eLORETA cortical rhythms between AD groups stratified in terms of ‘Normal’ and ‘High’ non-Cp-Cu. Results: The High non-Cp-Cu group experienced a lower power in all bands (0.2-48 Hz) in the parietal cortices (p=0.019) and a more limited alpha band (8-13 Hz) power in the sensory lobes (temporal, occipital, and parietal p<0.05 consistently) than the Normal non-Cp-Cu AD group. When corrected for MMSE, the non-Cp-Cu levels correlated with a reduction of high-frequency brain activity (from high alpha to gamma, 10.5-48 Hz). Conclusion: This neurophysiological heterogeneity in EEG-derived brain cortical rhythms between the two AD groups sustains a copper AD metabolic subtype; Non-Cp-Cu is a marker of this copper AD.

Original languageEnglish
Pages (from-to)1374-1384
Number of pages11
JournalCurrent Alzheimer Research
Issue number12
Publication statusPublished - Dec 1 2016


  • Alzheimer’s disease (AD) subtype
  • Ceruloplasmin
  • Cortical lobes
  • Electroencephalography (EEG)
  • Free copper

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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