Non-Ceruloplasmin Copper as a Stratification Biomarker of Alzheimer’s Disease Patients: How to Measure and Use It

Alzheimer’s Disease (AD) is a type of dementia very common in the elderly. A growing body of recent evidence has linked AD pathogenesis to Copper (Cu) dysmetabolism in the body. In fact, a subset of patients affected either by AD or by its prodromal form known as Mild Cognitive Impairment (MCI) have been observed to be unable to maintain a proper balance of Cu metabolism and distribution and are characterized by the presence in their serum of increased levels of Cu not bound to ceruloplasmin (non-ceruloplasmin Cu). Since serum non-ceruloplasmin Cu is a biomarker of Wilson's Disease (WD), a well-known condition of Cu-driven toxicosis, in this review, we propose that in close analogy with WD, the assessment of non-ceruloplasmin Cu levels can be exploited as a cost-effective stratification and susceptibility/risk biomarker for the identification of some AD/MCI individuals. The approach can also be used as an eligibility criterion for clinical trials aiming at investigating Cu-related interventions against AD/MCI.