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Modification of amyloid-β1-42 fibril structure by methionine-35 oxidation

Liming Hou1, Hyoung-Gon Lee, Fang Han

  • 1Abbott Vascular Inc., Menlo Park, CA, USA.

Journal of Alzheimer'S Disease : JAD
|May 31, 2013
PubMed

Insights

Oxidation of methionine-35 in amyloid-beta peptides alters the structure and stability of amyloid plaques. This finding links oxidative stress and Alzheimer's disease plaque formation, impacting neurotoxicity.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Alzheimer's disease (AD) involves oxidative stress and amyloid-beta (Aβ) plaque formation.
  • The methionine-35 (Met35) residue of Aβ is crucial in AD's oxidative stress and neurotoxicity.
  • Previous studies showed Met35 oxidation inhibits Aβ assembly into protofibrils.

Purpose of the Study:

  • To investigate how Met35 oxidation state affects the stability of pre-existing amyloid fibrils and plaques.
  • To determine the impact of Met35 oxidation on the morphology of AD pathological structures.

Main Methods:

  • Studied the effect of Met35 oxidation (Met35red → Met35ox) on isolated amyloid fibrils and senile plaques from AD patient brains.
  • Analyzed morphological changes in filaments, protofibrils, and mature fibrils.
  • Assessed Congo red birefringence in senile plaques.

Main Results:

  • Met35 oxidation altered the morphology of amyloid structures, including fibrils, protofibrils, and mature fibrils.
  • Oxidation led to a loss of Congo red birefringence in senile plaques.
  • Fibrils exhibited increased flexibility, changing from straight to irregularly shaped, rope-like structures.

Conclusions:

  • The oxidation state of Met35 significantly impacts the stability and morphology of existing amyloid plaques.
  • Findings suggest a strong link between Met35 oxidation and the formation and characteristics of amyloid plaques in Alzheimer's disease.

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