Elevation of serum copper levels in Alzheimer's disease.
OBJECTIVE
To determine whether serum trace metals and oxidative species are related to abnormal cognition in AD.


METHODS
The authors studied serum peroxides, copper, iron, transferrin, and antioxidant capacity in 79 patients with AD (mean age 74.3 years; 25 men, 54 women) and in 76 cognitively normal individuals (mean age 70.1 years; 33 men, 43 women). The relation of these oxidative and trace metals to APOE epsilon4 allele frequency, neuropsychological performance, and cerebrovascular or atrophic burden, as estimated by brain MRI and ultrasonography of cerebral vessels, was evaluated.


RESULTS
Copper level was higher (p < 0.001) in subjects with AD than control subjects (specificity = 95%, sensitivity = 60%) with a cutoff serum level of 16 micro mol/L (1.02 mg/L). An increase of 1 micro mol/L in serum copper accounted for 80% of the risk of having AD and correlated with poor neuropsychological performance and medial temporal lobe atrophy (p < 0.03). Antioxidant capacity decreased and correlated with medial temporal lobe atrophy (p < 0.009) and with APOE epsilon4 allele (p = 0.004).


CONCLUSIONS
Copper may play a role in neurodegenerative processes in AD, and serum copper measurement may prove to be a peripheral diagnostic marker for AD.
Squitti
R
R
Department of Neuroscience, AFaR-Ospedale Fatebenefratelli, 00186, Rome, Italy. squitti@iess.rm.cnr.it
Lupoi
D
D
Pasqualetti
P
P
Dal Forno
G
G
Vernieri
F
F
Chiovenda
P
P
Rossi
L
L
Cortesi
M
M
Cassetta
E
E
Rossini
P M
PM
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003300:Copper / Q000097:blood*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010545:Peroxides / Q000097:blood; D018709:Statistics, Nonparametric; D014463:Ultrasonography
D015415:Biomarkers; D010545:Peroxides; D003300:Copper