Effect of copper intake on CSF parameters in patients with mild Alzheimer's disease: a pilot phase 2 clinical trial

A plethora of reports suggest that copper (Cu) homeostasis is disturbed in Alzheimer's disease (AD). In the present report we evaluated the efficacy of oral Cu supplementation on CSF biomarkers for AD. In a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial (12 months long) patients with mild AD received either Cu-(II)-orotate-dihydrate (verum group; 8 mg Cu daily) or placebo (placebo group). The primary outcome measures in CSF were A beta 42, Tau and Phospho-Tau. The clinical trial demonstrates that long-term oral intake of 8 mg Cu can be excluded as a risk factor for AD based on CSF biomarker analysis. Cu intake had no effect on the progression of Tau and Phospho-Tau levels in CSF. While A beta 42 levels declined by 30% in the placebo group (P = 0.001), they decreased only by 10% (P = 0.04) in the verum group. Since decreased CSF A beta 42 is a diagnostic marker for AD, this observation may indicate that Cu treatment had a positive effect on a relevant AD biomarker. Using mini-mental state examination (MMSE) and Alzheimer disease assessment scale-cognitive subscale (ADAS-cog) we have previously demonstrated that there are no Cu treatment effects on cognitive performance, however. Finally, CSF A beta 42 levels declined significantly in both groups within 12 months supporting the notion that CSF A beta 42 may be valid not only for diagnostic but also for prognostic purposes in AD.