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Selection of Aptamers for Amyloid β-Protein, the Causative Agent of Alzheimer's Disease
Published on: May 13, 2010
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A genetically encoded selection for amyloid-β oligomer binders.
ByungUk Lee1, John A Mannone1, Tina Wang2
1Department of Chemistry, University of Wisconsin-Madison, Madison, WI, USA.
Nature Chemical Biology
|July 15, 2025
Summary
Researchers developed a biosensor to detect toxic amyloid-β oligomers (AβOs) in Alzheimer disease. This tool rapidly identifies potent binding proteins, accelerating the discovery of new diagnostics and therapeutics for neurodegenerative diseases.
Area of Science:
- Neuroscience
- Biochemistry
- Molecular Biology
Background:
- Soluble amyloid-β oligomers (AβOs) are implicated in Alzheimer disease neurotoxicity.
- Identifying specific binders to transient AβOs is difficult due to their short lifespan and low concentration.
- Existing methods face challenges in detecting AβOs generated during the aggregation cascade.
Purpose of the Study:
- To develop a novel strategy for detecting binding to AβOs.
- To enable rapid and reproducible measurement of AβO binder activity.
- To facilitate the selection of new, high-potency AβO binders.
Main Methods:
- Utilized a genetically encoded biosensor to detect AβOs.
- Applied the biosensor to Aβ42 aggregation process.
- Measured the activity of existing and novel AβO binders.
Main Results:
- Demonstrated rapid and reproducible measurement of AβO binder activity.
- Identified novel binders with >20-fold greater potency than reported binders.
- Showcased the ability to select for improved binder potency.
Conclusions:
- The genetically encoded biosensor strategy accelerates the discovery of AβO binding proteins.
- This approach enhances the characterization of binders targeting toxic AβOs.
- The findings may lead to improved diagnostic and therapeutic strategies for Alzheimer disease.
