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Aluminium, iron, zinc and copper influence the in vitro formation of amyloid fibrils of Aβ42 in a manner which may have consequences for metal chelation therapy in Alzheimer's disease
Abstract
Metals are found associated with beta-pleated sheets of Abeta42 in vivo and may be involved in their formation. Metal chelation has been proposed as a therapy for Alzheimer's disease on the basis that it may safely dissolve precipitated Abeta peptides. We have followed fibrillisation of Abeta42 in the presence of an additional metal ion (Al(III), Fe(III), Zn(II), Cu(II)) over a period of 32 weeks and we have investigated the dissolution of these aged peptide aggregates in the presence of both desferrioxamine (DFO) and ethylenediaminetetraacetic acid (EDTA). Abeta42 either alone or in the presence of Al(III) or Fe(III) formed beta-pleated sheets of plaque-like amyloids which were dissolved upon incubation with either chelator. Zn(II) inhibited whilst Cu(II) prevented the formation of beta-pleated sheets of Abeta42and neither of these influences were affected by incubation of the aged peptide aggregates with either DFO or EDTA. Freshly prepared solutions of Abeta42 either alone or in the presence of added Al(III) or Fe(III) did not form beta-pleated amyloid in the presence of DFO when incubated for up to 8 weeks. EDTA did not prevent beta-pleated amyloid formation in the same treatments and promoted beta-pleated amyloid formation in the presence of either Zn(II) or Cu(II). The presence of significant concentrations of Al(III) and Fe(III) as contaminants of 'Abeta42 only' preparations suggested that both of these metals were involved in either triggering the formation or stabili…
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“Exley et al. have used fluorescence assays and transmission electron microscopy (TEM) to show that both sub- and superstoichiometric concentrations of Cu2+ prevent aggregation of Aβ42 into thioflavin T (ThT)-positive β-sheet-rich amyloid fibrils.17−19”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [17]
In the citing paper
“while Cu2+ by itself is not toxic to N2A cells, the presence of Cu2+ and either monomeric Aβ42 or soluble Aβ42 oligomers exhibits enhanced cell toxicity.17,18”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [17]
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Metadata
- Authors
- House, E., Collingwood, J., Khan, A., Korchazkina, O., Berthon, G., & Exley, C.
- Affiliations
- Keele University (GB)
- Centre for Science and Technology in Medicine, Keele University, Staffordshire, UK
- Université Toulouse III - Paul Sabatier (FR)
- Corresponding author
- Exley, Christopher
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2004-06-03
- Volume
- 6
- Issue
- 3
- Pages
- 291-301
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W1480108665
- Cited by
- 294
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 8 · 2021: 17 · 2020: 15 · 2019: 20 · 2018: 16 · 2017: 16 · 2016: 9 · 2015: 16 · 2014: 8 · 2013: 15 · 2012: 27
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01 AG02030-01 A1)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- amyloid-beta 42, metal ions
- MeSH terms
- Aluminum, Alzheimer Disease, Brain, Chromatography, High Pressure Liquid, Copper, Edetic Acid, Humans, Iron, Peptide Fragments, Zinc, Chelation Therapy, Amyloid beta-Peptides, In Vitro Techniques
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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