Serum Iron, Zinc, and Copper Levels in Patients with Alzheimer’s Disease: A Replication Study and Meta-Analyses

Article type: Research Article

Authors: Wang, Zi-Xuan^a | Tan, Lan^{a; b; *} | Wang, Hui-Fu^b | Ma, Jing^a | Liu, Jinyuan^c | Tan, Meng-Shan^a | Sun, Jia-Hao^a | Zhu, Xi-Chen^b | Jiang, Teng^d | Yu, Jin-Tai^{a; b; e; *}

Affiliations: [a] Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, Shandong Province, China | [b] Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Nanjing, China | [c] Columbia College, Columbia University, USA | [d] Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China | [e] Memory and Aging Center, Department of Neurology, University of California, San Francisco, USA

Correspondence: [*] Correspondence to: Lan Tan, MD, PhD, Department of Neuro-logy, Qingdao Municipal Hospital, School of Medicine, QingdaoUniversity, No. 5 Donghai Middle Road, Qingdao, Shandong Province 266071, China. dr.tanlan@163.com

Correspondence: [*] Correspondence to: Jin-Tai Yu, Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA 94158, USA. Tel./Fax: +86 532 8890 5659; yu-jintai@163.com or jintai.yu@ucsf.edu (J.T. Yu).

Abstract: To evaluate whether iron, zinc, and copper levels in serum are disarranged in Alzheimer’s disease (AD), we performed meta-analyses of all studies on the topic published from 1984 to 2014 and contextually carried out a replication study in serum as well. Our meta-analysis results showed that serum zinc was significantly lower in AD patients. Our replication and meta-analysis results showed that serum copper was significantly higher in AD patients than in healthy controls, so our findings were consistent with the conclusions of four previously published copper meta-analyses. Even if a possible role of iron in the pathophysiology of the disease could not be ruled out, the results of our meta-analysis showed no change of serum iron levels in AD patients, but this conclusion was not robust and requires further investigation. The meta-regression analyses revealed that in some studies, differences in serum iron levels could be due to the different mean ages, while differences in zinc levels appeared to be due to the different sex ratios. However, the effect of sex ratio on serum zinc levels in our meta-analysis is subtle and needs further confirmation. Also, diverse demographic terms and methodological approaches appeared not to explain the high heterogeneity of our copper meta-analysis. Therefore, when investigating trace elements, covariants such as age and sex have to be taken into account in the analyses. In the light of these findings, we suggest that the possible alteration of serum zinc and copper levels are involved in the pathogenesis of AD.

Keywords: Alzheimer’s disease, meta-analysis, serum copper, serum iron, serum zinc

DOI: 10.3233/JAD-143108

Journal: Journal of Alzheimer's Disease, vol. 47, no. 3, pp. 565-581, 2015