Evidence map›Paper›PMID 21600264›Full record

SynthesisProgress in neurobiology2011

Iron, zinc and copper in the Alzheimer's disease brain: a quantitative meta-analysis. Some insight on the influence of citation bias on scientific opinion.

Matthew Schrag, Claudius Mueller, Udochukwu Oyoyo, Mark A Smith, Wolff M Kirsch

Abstract readMeta-Analysis
In one paragraph

Synthesis in Progress in neurobiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 3 pooled it
14.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

107 citing papers in PubMed, 3 syntheses or guidelines pooled it, 260 citations in OpenAlex.

  1. Are high copper levels related to Alzheimer's and Parkinson's diseases? A systematic review and meta-analysis of articles published between 2011 and 2022.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024
    Pooled it
  2. Pooled it
  3. Pooled it
  4. Article
  5. Review
  6. Article
  7. Environmental toxins in neurodegeneration - a narrative review.Neurological research and practice · 2025
    Review
  8. Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025
    Review
  9. Review
  10. A primer on copper biology in the brain.Neurobiology of disease · 2025
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. An N-terminal acidic β-sheet domain is responsible for the metal-accumulation properties of amyloid-β protofibrils: a molecular dynamics study.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2024
    Article
  16. HFE Mutations in Neurodegenerative Disease as a Model of Hormesis.International journal of molecular sciences · 2024
    Review
  17. Review
  18. Article
  19. Article
  20. Article

47 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Matthew SchragNeurosurgery Center for Research, Training and Education, Loma Linda University, Loma Linda, CA, USA. mschrag@llu.edu
Claudius Mueller
Udochukwu Oyoyo
Mark A Smith
Wolff M Kirsch
Loma Linda University · USCase Western Reserve University · US

Funding

Iron Metabolism Alterations in Alzheimer's DiseaseR01AG020948 · NIA · LOMA LINDA UNIVERSITY · PI KIRSCH, WOLFF M. · 2002 to 2006
$6.5M
NIA NIH HHS AG20948NIA NIH HHS R01 AG020948
6 · The paper itself

Abstract

Dysfunctional homeostasis of transition metals is believed to play a role in the pathogenesis of Alzheimer's disease (AD). Although questioned by some, brain copper, zinc, and particularly iron overload are widely accepted features of AD which have led to the hypothesis that oxidative stress generated from aberrant homeostasis of these transition metals might be a pathogenic mechanism behind AD. This meta-analysis compiled and critically assessed available quantitative data on brain iron, zinc and copper levels in AD patients compared to aged controls. The results were very heterogeneous. A series of heavily cited articles from one laboratory reported a large increase in iron in AD neocortex compared to age-matched controls (p<0.0001) while seven laboratories failed to reproduce these findings reporting no significant difference between the groups (p=0.76). A more than three-fold citation bias was found to favor outlier studies reporting increases in iron and this bias was particularly prominent among narrative review articles. Additionally, while zinc was not significantly changed in the neocortex (p=0.29), copper was significantly depleted in AD (p=0.0003). In light of these findings, it will be important to re-evaluate the hypothesis that transition metal overload accounts for oxidative injury noted in AD.

Indexed as

BiasPeriodicals as TopicAlzheimer DiseaseCopperDatabases, FactualHomeostasisHumansIronMiddle AgedOxidative StressZincCopperIronZinc

Identifiers

PMID21600264
PMCPMC3134620
OpenAlexW1969041362

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.