Sensitive ELISA detection of amyloid‐β protofibrils in biological samples
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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Aducanumab has a normalized rate of amyloid removal of 5.5 CL/4 wk/10mg/kg.
“| Aducanumab | 6 3 | 64 d /109 | 67 2 | 78 | 5.5 | 35 | 6.4 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [115]
Aducanumab has an incidence of ARIA-E of 35%.
“| Aducanumab | 6 3 | 64 d /109 | 67 2 | 78 | 5.5 | 35 | 6.4 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [115]
Aducanumab has an ARIA-E/amyloid removal rate index of 6.4.
“| Aducanumab | 6 3 | 64 d /109 | 67 2 | 78 | 5.5 | 35 | 6.4 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [115]
Aducanumab removes 64 centiloids in 109 patients.
“| Aducanumab | 6 3 | 64 d /109 | 67 2 | 78 | 5.5 | 35 | 6.4 |”
From The amyloid hypothesis in Alzheimer disease: new insights from new therapeutics (2022) · cites this paper as [115]
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Self-citation
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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