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CE-ICP-MS to probe Aβ1-42/copper (II) interactions, a complementary tool to study amyloid aggregation in Alzheimer's
1Université de Lyon, CNRS, Université Claude Bernard Lyon 1, Institut des Sciences Analytiques, UMR 5280, 69100 Villeurbanne, France.
Metallomics : Integrated Biometal Science
|December 24, 2021
Summary
Copper (II) ions influence Alzheimer's disease peptide aggregation. This study used CE-ICP-MS to show copper enhances aggregation and affects pathways, clarifying its role in amyloid-β1-42 peptide clumping.
Area of Science:
- Neuroscience
- Biochemistry
- Analytical Chemistry
Background:
- Copper (II) ions are implicated in Alzheimer's disease pathogenesis.
- The role of copper (II) in amyloid-β1-42 (Aβ1-42) peptide aggregation is debated, with conflicting evidence suggesting both promotion and inhibition.
- Understanding copper's precise influence is crucial for developing therapeutic strategies.
Purpose of the Study:
- To investigate the effect of copper (II) ions on Aβ1-42 aggregation.
- To elucidate the distribution and speciation of copper during Aβ1-42 aggregation.
- To clarify the role of copper in Alzheimer's disease-related peptide aggregation.
Main Methods:
- Utilized capillary electrophoresis-inductively coupled plasma-mass spectrometry (CE-ICP-MS) hyphenation.
- Analyzed copper distribution in different Aβ1-42 oligomeric forms.
- Studied varying substoichiometries and incubation times of copper with Aβ1-42.
Main Results:
- Observed the formation of multiple negatively charged copper complexes.
- Demonstrated an enhanced Aβ1-42 aggregation rate with increasing copper concentration.
- Identified variations in copper (II) speciation, suggesting distinct aggregation pathways even at substoichiometric ratios.
Conclusions:
- Copper (II) ions promote the aggregation of Aβ1-42 peptide.
- CE-ICP-MS is an effective tool for tracking copper speciation during peptide aggregation.
- Copper's influence on aggregation pathways may vary depending on its concentration and speciation.
