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Cited by 221Alzheimer's disease research and treatmentsPrion Diseases and Protein MisfoldingAmyloidosis: Diagnosis, Treatment, Outcomes

Neurotoxic protein oligomers — what you see is not always what you get

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Bitan, Gal, Fradinger, Erica A, Spring, Sean M, Teplow, David B·2005·Amyloid
DOI 10.1080/13506120500106958
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Abstract

An increasing body of evidence suggests that soluble assemblies of amyloid proteins are the predominant neurotoxic species in many amyloid-related diseases. Consequently, the focus of research on pathologic mechanisms underlying amyloidoses has shifted from amyloid fibrils to oligomers. Biophysical characterization of oligomers is difficult due to their metastable nature. The most popular experimental method for detection of oligomers has been SDS-PAGE. However, we provide experimental evidence that SDS-PAGE is not a reliable method for characterization of amyloid protein oligomers and discuss alternative approaches. In addition, we discuss how inconsistent nomenclature has obfuscated our understanding of the process and products of protein assembly. The goals of this paper are to identify pitfalls associated with the methods and language used to study protein oligomers and to provide alternatives, thereby facilitating successful elucidation of the mechanisms controlling amyloid protein oligomer assembly and toxicity.

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  • Aβ40 does not form oligomers either in the presence or absence of metal ions.

    “Notably, the Aβ40 peptide does not form oligomers either in presence or in absence of metal ions (Fig. 2, lanes a–c), a similar behavior being observed for Aβ40 by SDS-PAGE.49”

    From The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity (2013) · cites this paper as [49]

    The section ‘SDS-PAGE induces formation of high molecular weight Aβ assemblies’ reports that Aβ40 migrated as a monomer on SDS-PAGE, supporting the cited comparison of gel behavior. It does not establish that Aβ40 cannot form oligomers with or without metal ions. The section on SDS- and non-SDS-based methods describes cross-linked Aβ40 oligomers and cautions that SDS-PAGE can misrepresent oligomerization state. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Bitan, G., Fradinger, E. A., Spring, S. M., & Teplow, D. B.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Bitan, Gal
ORCID
Venue
Amyloid
Publisher
Informa UK Limited
Published
2005-06
Volume
12
Issue
2
Pages
88-95
ISSN
  • 1350-6129 (ISSN-L)
  • 1744-2818
DOI
10.1080/13506120500106958
OpenAlex
W2052647401
Cited by
221
References
7
Citations by year
2026: 2 · 2025: 6 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 10 · 2020: 2 · 2019: 7 · 2018: 10 · 2017: 11 · 2016: 10 · 2015: 19 · 2014: 13 · 2013: 24 · 2012: 21
FWCI
5.42
Type
journal article
Language
en
Open access
Locations
  • Amyloid (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • American Foundation for Aging Research
  • National Institutes of Health
  • National Institute on Aging (AG 18921, R01AG018921)
  • National Institute of Neurological Disorders and Stroke (R01NS038328, NS38328, NS44147, R01NS044147)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Amyloidosis: Diagnosis, Treatment, Outcomes
Keywords
protein oligomers, amyloidosis, neurotoxicity, amyloid fibrils, protein assembly, nomenclature, amyloidosis pathogenesis
MeSH terms
Biopolymers, Chromatography, Gel, Electrophoresis, Polyacrylamide Gel, Molecular Weight, Nervous System, Terminology as Topic, Proteins

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