Levels of iron and iron-related proteins in Alzheimer's disease: A systematic review and meta-analysis

Iron homeostasis disturbance has been suggested to play a role in the pathology of Alzheimer's disease (AD). Systemic iron levels are regulated by iron-related proteins, such as ferritin and transferrin. This meta-analysis was established to evaluate iron and iron-related proteins (ferritin, transferrin, lactoferrin, haptoglobin, hepcidin) in cerebrospinal fluid (CSF) and blood samples of AD patients compared with those in healthy controls (HCs).

Iron and iron-related proteins in Alzheimer's disease was systematically searched within five databases (PubMed, EMBASE, Web of Science, Cochrane, Scopus) up to October 23, 2022. Fifty-four studies (with data for 5105 participants: 2174 AD patients and 2931 HCs) were included in this meta-analysis. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), applying Stata 14.0 software.

Decreased iron in blood and increased ferritin in CSF were found in AD patients compared with the levels in HCs. AD patients also exhibited lower lactoferrin in serum. Other variables (iron in CSF, ferritin in blood, transferrin in CSF/blood, haptoglobin in CSF/blood, and hepcidin in blood) did not differ between the groups.

This meta-analysis indicated that iron and iron-related proteins were associated with the risk of AD, suggesting the value of further exploration of iron imbalance in AD using biofluids.