A Strategy for Designing a Peptide Probe for Detection of β-Amyloid Oligomers

Authors

  • Yang Hu,

    1. Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201 (USA), Fax: (+1) 718-260-3125
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  • Baihao Su,

    1. Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201 (USA), Fax: (+1) 718-260-3125
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  • Dr. Chung-Sei Kim,

    1. Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201 (USA), Fax: (+1) 718-260-3125
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  • Michael Hernandez,

    1. Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201 (USA), Fax: (+1) 718-260-3125
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  • Prof. Agueda Rostagno,

    1. Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016 (USA)
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  • Prof. Jorge Ghiso,

    1. Department of Pathology, New York University School of Medicine, 550 First Avenue, New York, NY 10016 (USA)
    2. Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, NY 10016 (USA)
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  • Prof. Jin Ryoun Kim

    Corresponding author
    1. Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201 (USA), Fax: (+1) 718-260-3125
    • Othmer-Jacobs Department of Chemical and Biological Engineering, Polytechnic Institute of New York University, 6 MetroTech Center, Brooklyn, NY 11201 (USA), Fax: (+1) 718-260-3125
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Abstract

Aggregation of β-amyloid (Aβ) is implicated in the pathology of Alzheimer's disease. Development of a robust strategy to detect Aβ oligomeric intermediates, which have been identified as significant toxic agents, would be highly beneficial in the screening of drug candidates as well as enhancing our understanding of Aβ oligomerization. Rapid, specific and quantitative detection, currently unavailable, would be highly preferred for accurate and reliable probing of transient Aβ oligomers. Here, we report the development of a novel peptide probe, PG46, based on the nature of Aβ self-assembly and the conformation-sensitive fluorescence of the biarsenical dye, FlAsH. PG46 was found to bind to Aβ oligomers and displayed an increase in FlAsH fluorescence upon binding. No such event was observed when PG46 was co-incubated with Aβ low-molecular-weight species or Aβ fibrils. Aβ oligomer detection was fast, and occurred within one hour without any additional sample incubation or preparation. We anticipate that the development of a strategy for detection of amyloid oligomers described in this study will be directly relevant to a host of other amyloidogenic proteins.

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