Improperly folded metal proteins, for example, CCS or Cu-Zn-superoxide dismutase (SOD1) present in brain, blood or other clinical samples, are indicative of neurodegenerative diseases like Alzheimer's disease (AD) or amyotrophic lateral sclerosis (ALS). Active CCS or SOD molecules contribute to intracellular homeostatic control of essential metal ions (e.g., Cu, Zn, Fe, Mn, Ni) in organisms, and thus, these biomolecules can balance pro-oxidative and antioxidative processes in the cytoplasm. Otherwise, free or loosely bound transition metal ions take part in Fenton-like reactions in which deleterious hydroxyl radical is formed, which unrestrained would be destructive to proteins. The loss of active CCS increases the amyloid-β production in neurons which, in turn, is a major pathological hallmark of AD. Therefore, copper chaperone for superoxide dismutase is proposed to be one of the most promising biomarkers of Cu toxicity in these diseases. CCS should be analysed primarily in blood because a meta-analysis of serum data showed that AD patients have higher levels of serum Cu than healthy controls.