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Non-Ceruloplasmin Copper Distinguishes A Distinct Subtype of Alzheimer’s Disease: A Study of EEG-Derived Brain Activity

[ Vol. 13 , Issue. 12 ]


Franca Tecchio, Fabrizio Vecchio, Mariacarla Ventriglia, Camillo Porcaro, Francesca Miraglia, Mariacristina Siotto, Paolo M. Rossini, Mauro Rongioletti and Rosanna Squitti   Pages 1374 - 1384 ( 11 )


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.


Alzheimer's disease (AD) subtype, ceruloplasmin, cortical lobes, Electroencephalography (EEG), free copper.


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