title: Perturbed iron distribution in Alzheimer's disease serum, cerebrospinal fluid, and selected brain regions: a systematic review and meta-analysis.
abstract: 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).
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratory of Nutrition and Metabolism, Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Neurochemistry Laboratory, Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: Jack T
authors.initials: JT
authors.lastname: Rogers
authors.affiliation: Laboratory of Nutrition and Metabolism, Department of Nutrition, Research Center for Nutrition and Health, Institute of Nutrition and Food Safety, School of Public Health, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Fudi
authors.initials: F
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D001921:Brain / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D019189:Iron Metabolism Disorders / Q000378:metabolism / Q000473:pathology
chemical_list: D007501:Iron
keywords: Alzheimer's disease; cerebrospinal fluid; iron; iron overload; meta-analysis; serum iron; systematic review