Extracellular phosphorylation of the amyloid beta-peptide promotes formation of toxic aggregates during the pathogenesis of Alzheimer's disease
2011

Phosphorylation of Amyloid Beta Peptides and Alzheimer's Disease

publication Evidence: moderate

Author Information

Author(s): Kumar Sathish, Walter Jochen

Primary Institution: University of Bonn

Hypothesis

Phosphorylation of amyloid beta (Aβ) peptides may trigger the formation of toxic aggregates in Alzheimer's disease.

Conclusion

Phosphorylation of Aβ promotes the formation of toxic aggregates that could play a significant role in the pathogenesis of Alzheimer's disease.

Supporting Evidence

  • Phosphorylated Aβ was detected in the brains of transgenic mice and human AD brains.
  • Phosphorylation of Aβ increased its toxicity in Drosophila models compared to non-phosphorylated Aβ.
  • Phosphorylation promotes the formation of oligomeric Aβ aggregates that serve as nuclei for fibrillization.

Takeaway

When certain proteins in the brain get a chemical tag called phosphorylation, they can clump together and become harmful, which might be a big part of what causes Alzheimer's disease.

Methodology

The study involved in vitro and in vivo experiments using transgenic Drosophila models to assess the effects of Aβ phosphorylation on toxicity and aggregation.

Limitations

The study primarily focuses on the role of phosphorylation without exploring other potential factors influencing Aβ aggregation.

Digital Object Identifier (DOI)

10.1038/emboj.2011.155

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