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

Abstract

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

Methods: The authors studied copper, ceruloplasmin, total peroxide, and antioxidants levels (TRAP) in serum; β-amyloid in plasma; and copper, β-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 β-amyloid were decreased (p < 0.0001). Plasma β-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 β-amyloid seemed to be related to serum copper (r = −0.46; p = 0.002). Mini-Mental Status Examination scores correlated positively with β-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 β-amyloid and copper connection in Alzheimer disease.