Cited by 292Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Sensitive ELISA detection of amyloid‐β protofibrils in biological samples

Englund, Hillevi, Sehlin, Dag, Johansson, Ann‐Sofi, Nilsson, Lars N. G., Gellerfors, Pär, Paulie, Staffan, Lannfelt, Lars, Pettersson, Frida Ekholm·2007·Journal of Neurochemistry

Abstract

Amyloid‐β (Aβ) protofibrils are known intermediates of the in vitro Aβ aggregation process and the protofibrillogenic Arctic mutation (APPE693G) provides clinical support for a pathogenic role of Aβ protofibrils in Alzheimer’s disease (AD). To verify their in vivo relevance and to establish a quantitative Aβ protofibril immunoassay, Aβ conformation dependent monoclonal antibodies were generated. One of these antibodies, mAb158 (IgG2a), was used in a sandwich ELISA to specifically detect picomolar concentrations of Aβ protofibrils without interference from Aβ monomers or the amyloid precursor protein (APP). The specificity and biological significance of this ELISA was demonstrated using cell cultures and transgenic mouse models expressing human APP containing the Swedish mutation (APPKN670/671ML), or the Swedish and Arctic mutation in combination. The mAb158 sandwich ELISA analysis revealed presence of Aβ protofibrils in both cell and animal models, proving that Aβ protofibrils are formed not only in vitro, but also in vivo. Furthermore, elevated Aβ protofibril levels in the Arctic‐Swedish samples emphasize the usefulness of the Arctic mutation as a model of enhanced protofibril formation. This assay provides a novel tool for investigating the role of Aβ protofibrils in AD and has the potential of becoming an important diagnostic assay.

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Crossref · 10.1111/j.1471-4159.2007.04759.x

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Authors
Englund, H., Sehlin, D., Johansson, A., Nilsson, L. N. G., Gellerfors, P., Paulie, S., Lannfelt, L., & Pettersson, F. E.
Affiliations
  • Uppsala University (SE)
  • Mabtech (Sweden) (SE)
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2007-06-09
Volume
103
Issue
1
Pages
334-345
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
OpenAlex
W2085804617
Cited by
292
References
59
Citations by year
2026: 26 · 2025: 32 · 2024: 35 · 2023: 30 · 2022: 18 · 2021: 16 · 2020: 11 · 2019: 8 · 2018: 10 · 2017: 17 · 2016: 9 · 2015: 10 · 2014: 9 · 2013: 13 · 2012: 11
FWCI
6.23
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
amyloid-beta protofibrils, amyloid-beta aggregation, Alzheimer's disease, Arctic mutation, Swedish mutation, sandwich ELISA, amyloid precursor protein, transgenic mouse model, diagnostic assay
MeSH terms
Alzheimer Disease, Amyloid, Animals, Antibodies, Monoclonal, Antibody Specificity, Cell Line, Enzyme-Linked Immunosorbent Assay, Humans, Immunoenzyme Techniques, Mice, Transgenic, Mutation, Sensitivity and Specificity, Amyloid beta-Protein Precursor, Mice

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