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 ε4 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 μmol/L (1.02 mg/L). An increase of 1 μmol/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 ε4 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.