Circulatory trace element variations in Alzheimer’s disease: a systematic review and meta-analysis

Trace element levels in the circulation (blood, serum, plasma) are believed to play a role in the pathophysiologic processes of Alzheimer’s disease (AD); however, there is heterogeneity in the available findings. This study conducted a systematic review and meta-analysis of trace elements (including: copper (Cu), iron (Fe), zinc (Zn), selenium (Se), lead (Pb), cadmium (Cd), mercury (Hg), manganese (Mn), aluminum (Al), arsenic (As), and magnesium (Mg)) in AD patients and controls to assess the variation of trace elements in the circulation of AD patients. By systematically screening case–control studies on circulatory trace element levels in AD patients from 2000 to the present in the PubMed, Web of Science, and MEDLINE databases, 52 studies were included in the final meta-analysis. The results of the random-effects model showed significantly elevated circulatory levels of Cd (SMD = 0.79, 95% CI: 0.35, 1.24), Hg (SMD = 0.59, 95% CI: 0.03, 1.16), and Cu (SMD = 0.70, 95% CI: 0.37, 1.04) in AD patients, while levels of Fe (SMD = − 0.58, 95% CI: − 1.03, − 0.13), Se (SMD = − 0.53, 95% CI: − 0.85, − 0.21), and Zn (SMD = − 0.99, 95% CI: − 1.52, − 0.46) were significantly lower. The database formed in this study provides reliable population-based research evidence for exploring changes in circulating trace element levels in AD patients. Monitoring and stabilization of circulatory trace element levels in the elderly may be a potential preventive target for AD.