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Neurology 2002;59:1153-1161
© 2002 American Academy of Neurology

Elevation of serum copper levels in Alzheimer’s disease

R. Squitti, PhD, D. Lupoi, MD, P. Pasqualetti, PhD, G. Dal Forno, MD, F. Vernieri, MD, P. Chiovenda, PhD, L. Rossi, PhD, M. Cortesi, MD, E. Cassetta, MD and P. M. Rossini, MD

From the Departments of Neuroscience (Drs. Squitti, Pasqualetti, Vernieri, Chiovenda, Cassetta, and Rossini), Radiology (Dr. Lupoi), and Laboratory Medicine (Dr. Cortesi), AFaR–Ospedale Fatebenefratelli, Rome; Department of Biology (Dr. Rossi), Tor Vergata University, Rome; IRCCS "Centro S. Giovanni di Dio-FBF" (Dr. Rossini), Brescia; and Clinica Neurologica (Drs. Dal Forno and Rossini), Università Campus Biomedico, Rome, Italy; and Department of Neurology (Dr. Dal Forno), Johns Hopkins University School of Medicine, Baltimore, MD.

Address correspondence and reprint requests to Dr. Rosanna Squitti, Department of Neuroscience, AFaR–Ospedale Fatebenefratelli, 00186, Rome, Italy; e-mail: squitti{at}iess.rm.cnr.it

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 {epsilon}4 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 {epsilon}4 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.




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Correspondence:

Read all Correspondence

Elevation of serum copper levels in Alzheimer’s disease
Steven Brenner
Neurology Online, 22 Jan 2003 [Full text]
Reply to Letter to the Editor
Rosanna Squitti, et al.
Neurology Online, 22 Jan 2003 [Full text]

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