Abnormal Brain Iron Homeostasis in Human and Animal Prion Disorders
2009

Iron Imbalance in Prion Diseases

Sample size: 20 publication 15 minutes Evidence: high

Author Information

Author(s): Ajay Singh, Alfred Orina Isaac, Xiu Luo, Mohan Maradumane L., Mark L. Cohen, Fusong Chen, Qingzhong Kong, Jason Bartz, Neena Singh

Primary Institution: Case Western Reserve University

Hypothesis

Is there an imbalance of brain iron homeostasis in prion diseases that contributes to neurotoxicity?

Conclusion

Prion disease-affected brains show a state of iron deficiency despite increased total iron levels, likely due to sequestration in PrPSc-ferritin complexes.

Supporting Evidence

  • Prion disease-affected brains show increased total iron and redox-active iron.
  • Transferrin levels increase in diseased brains despite iron excess, indicating iron deficiency.
  • Sequestration of iron in PrPSc-ferritin complexes leads to cellular iron deficiency.

Takeaway

In prion diseases, the brain has too much iron but the cells can't use it, which can make the brain sick.

Methodology

The study analyzed brain tissues from humans, hamsters, and mice infected with prion diseases, measuring iron levels and related proteins.

Potential Biases

Potential bias due to the selection of samples from specific disease stages.

Limitations

The study primarily focuses on end-stage disease samples, which may not represent earlier disease stages.

Participant Demographics

The study included human, hamster, and mouse brain samples, with a focus on sporadic Creutzfeldt-Jakob disease (sCJD) cases.

Statistical Information

P-Value

p<0.0001

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1371/journal.ppat.1000336

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