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The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes

Nature Neuroscience volume 15, pages 349–357 (2012)Cite this article

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Abstract

The 'toxic Aβ oligomer' hypothesis has attracted considerable attention among Alzheimer's disease researchers as a way of resolving the lack of correlation between deposited amyloid-β (Aβ) in amyloid plaques—in terms of both amount and location—and cognitive impairment or neurodegeneration. However, the lack of a common, agreed-upon experimental description of the toxic Aβ oligomer makes interpretation and direct comparison of data between different research groups impossible. Here we critically review the evidence supporting toxic Aβ oligomers as drivers of neurodegeneration and make some suggestions that might facilitate progress in this complex field.

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Figure 1: Generation of Aβ from amyloid precursor protein.
Figure 2: Size overlap in major natural and in vitro–generated Aβ oligomers.
Figure 3: Scheme of interconversion between different natural and synthetic Aβ assemblies based on pathways described in the literature.
Figure 4: Key steps of Aβ-initiated neurodegenerative cascade according to the amyloid hypothesis.
Figure 5: Molecular mechanisms of Aβ synaptotoxicity proposed in the literature.

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Acknowledgements

The authors acknowledge funding from the European Research Council (ERC); the Fund for Scientific Research, Flanders; the University of Leuven; the VIB; the Methusalem grant from the University of Leuven and the Flemish government; the Foundation for Alzheimer Research (SAO/FRMA); and the Interuniversity Attraction Poles Program. B.D.S. is the Arthur Bax and Anna Vanluffelen Chair for Alzheimer's Disease at the University of Leuven. The authors acknowledge T. Golde, D. Teplow, T. Härd and D. Walsh for fruitful discussions and/or sharing their amyloid-β preparations.

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  1. Center for Human Genetics and Leuven Institute for Neurodegenerative Diseases (LIND), University of Leuven, Leuven, Belgium

    Iryna Benilova, Eric Karran & Bart De Strooper

  2. VIB Center for the Biology of Disease, Leuven, Belgium

    Iryna Benilova & Bart De Strooper

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Supplementary Table 1

Conformation specific antibodies that react with oligomeric Aβ (PDF 228 kb)

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Benilova, I., Karran, E. & De Strooper, B. The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nat Neurosci 15, 349–357 (2012). https://doi.org/10.1038/nn.3028

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