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.