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Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF ß-amyloid, and h-tau

From the AFaR Departments of Neuroscience (R.W., G.B., M.V., S.C., F.M., I.C., E.C., P.P., P.M.R.) and Radiology (D.L.), Hospital Fatebenefratelli, Rome, Italy; Department of Biology (L.R.), Tor Vergata University, Rome, Italy; Department of Neurology (G.D.F.), Medical College of Wisconsin, Milwaukee, WI; Department of Biochemical Science (C.L.), "La Sapienza" University, Rome, Italy; IRCCS "Centro S. Giovanni di Dio-FBF" (P.M.R.), Brescia, Italy; Department of Neurology (P.M.R.), University "Campus Biomedico," Rome, Italy.

Address correspondence and reprint requests to Dr. Rosanna Squitti, AFaR Department of Neuroscience, AFaR Hospital Fatebenefratelli, 00186 Rome, Italy; e-mail: rosanna.squitti{at}afar.it

Objective: To assess whether serum copper in Alzheimer disease (AD) correlates with cognitive scores, ß-amyloid, and other CSF markers of neurodegeneration.

Methods: The authors studied copper, ceruloplasmin, total peroxide, and antioxidants levels (TRAP) in serum; ß-amyloid in plasma; and copper, ß-amyloid, h-tau, and P-tau in the CSF of 28 patients with AD and 25 healthy controls, in relation to clinical status.

Results: Serum copper (p < 0.0001), peroxides (p = 0.002), a copper fraction unexplained by ceruloplasmin (p < 0.0001), and CSF h-tau (p = 0.001) were increased in AD, whereas serum TRAP (p = 0.03) and CSF ß-amyloid were decreased (p < 0.0001). Plasma ß-amyloid increased with age in healthy controls (r = 0.6; p = 0.05). CSF markers of AD correlated with serum copper variables. CSF copper was partially dependent on the serum copper fraction unexplained by ceruloplasmin (t = 2.2, p = 0.04). CSF ß-amyloid seemed to be related to serum copper (r = –0.46; p = 0.002). Mini-Mental Status Examination scores correlated positively with ß-amyloid (r = 0.46, p = 0.002) and inversely with copper unexplained by ceruloplasmin (r = –0.45, p = 0.003).

Conclusions: The authors' results confirm the existence of changes in copper component distribution, particularly the copper fraction unexplained by ceruloplasmin and support the hypothesis of a ß-amyloid and copper connection in Alzheimer disease.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the July 11 issue to find the title link for this article.

Partially supported by grants ISPESL, PFA/DML/UO5/2001/AA "Malattia di Alzheimer: studio del rischio legato a fattori lavorativi" and by a grant from the AFaR Foundation Hospital Fatebenefratelli, Rome, Italy.

Disclosure: The authors report no conflicts of interest.

Received September 6, 2005. Accepted in final form March 20, 2006.

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