title: Non-Ceruloplasmin Copper Distinguishes A Distinct Subtype of Alzheimer's Disease: A Study of EEG-Derived Brain Activity.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.forename: Franca
authors.initials: F
authors.lastname: Tecchio
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vecchio
authors.forename: Mariacarla
authors.initials: M
authors.lastname: Ventriglia
authors.forename: Camillo
authors.initials: C
authors.lastname: Porcaro
authors.forename: Francesca
authors.initials: F
authors.lastname: Miraglia
authors.forename: Mariacristina
authors.initials: M
authors.lastname: Siotto
authors.forename: Paolo M
authors.initials: PM
authors.lastname: Rossini
authors.forename: Mauro
authors.initials: M
authors.lastname: Rongioletti
authors.affiliation: Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio- Fatebenefratelli, Via Pilastroni, 4, 25125 Brescia, Italy. rosanna.squitti@afar.it.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Squitti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000145:classification / Q000000981:diagnostic imaging / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D058256:Brain Waves / Q000502:physiology*; D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D015898:Tomography Scanners, X-Ray Computed
chemical_list: D001057:Apolipoproteins E; D003300:Copper; D002570:Ceruloplasmin