Peripheral serum copper metabolite levels measured by ultrafiltration aid in the clinical screening of Alzheimer’s disease

Background The number of patients with Alzheimer’s disease (AD) is increasing, yet misdiagnosis remains common and early accurate diagnosis is lacking. Previous studies have suggested abnormalities in peripheral serum copper levels in AD patients. This study sought to explore the diagnostic value of peripheral serum copper-related biomarkers for clinically diagnosed AD. Methods Peripheral serum samples were collected from 115 clinically diagnosed AD patients and 96 healthy controls (HC). A preliminary experiment on five samples determined the use of a 10 kDa ultrafiltration membrane. Four serum copper parameters—serum total copper (tot-Cu), free copper (free-Cu), serum immunological ceruloplasmin concentration (iCp), and ceruloplasmin enzymatic activity (eCp)—were quantitatively measured in all samples using ultrafiltration, atomic absorption spectrometry, and ELISA. Results Peripheral tot-Cu and free-Cu levels in clinically diagnosed AD patients were significantly elevated in the early stage of the disease, while iCp, eCp, and the iCp/eCp ratio were significantly decreased. The diagnostic efficacy of tot-Cu and free-Cu for these Alzheimer’s disease patients was significantly higher than that of the Mini-Mental State Examination (MMSE) score. Nevertheless, these indicators could not distinguish different severity stages of clinically phenotyped AD. Conclusion Our results indicate that tot-Cu or free-Cu holds promise as biomarkers for the clinical screening of AD; peripheral copper metabolic dysregulation may be involved in the pathogenesis of clinically phenotyped AD.