Perturbed Iron Distribution in Alzheimer's Disease Serum, Cerebrospinal Fluid, and Selected Brain Regions: A Systematic Review and Meta-Analysis

Background: The homeostasis and physiological role of iron in Alzheimer's disease (AD) has been debated for decades. Overall, it has been difficult to reach a consensus to prove marked disease-associated changes in the iron content of the AD brain, blood, or cerebrospinal fluid (CSF). Objectives: We sought to contribute to resolve this issue by quantifying the iron content in serum, CSF, and sub-regions of the AD brain. Methods: We conducted a comprehensive systematic meta-analysis and review of multiple observational studies till October 2013 that investigated the iron content in AD serum, CSF, or brain tissue. Results: 2,556 publications were screened. Forty-three eligible studies with 1,813 AD patients and 2,401 healthy controls were identified. Twenty-one studies investigated the serum iron in AD while seven and nineteen studies investigated the CSF iron and various brain regions iron respectively. Our meta-analysis showed that serum iron was significant lower in AD than healthy controls. CSF iron appeared not to be affected by AD although more studies are required due to the relative small number of CSF studies reported to date. We critically analyzed iron content in twelve selective brain regions by separated meta-analyses using cross-referenced statistical methods. We found that eight specific brain regions had higher iron concentrations that correlated with the clinical diagnosis of AD in a statistically validated manner. Conclusions: These data provided rigorous statistical support for the model that iron homeostasis was changed in AD patients, including the finding of lower iron in their serum and evidence for iron overload in several specific brain regions.