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Complement activation by the amyloid proteins Aβ peptide and β2-microglobulin
Abstract
Complement activation (CA) has been reported to play a role in the pathogenesis of Alzheimer's disease (AD). To investigate whether CA may contribute to amyloidogenesis in general, the CA potential of different amyloid fibril proteins was tested. CA induced by A beta preparations containing soluble protein, protofilaments and some fibrils or only fibrils in a solid phase system (ELISA) was modest with a slow kinetics compared to the positive delta IgG control. Soluble A beta induced no detectable CA in a liquid phase system (complement consumption assay) while fibrillar A beta caused CA at 200 mg/ml and higher concentrations. Soluble beta 2-microglobulin (beta 2M) purified from peritoneal dialysates was found to be as potent a complement activator as A beta in both solid and liquid phase systems while beta 2M purified from urine exhibited lower activity, a difference which may be explained by differences observed in SDS-resistant oligomers and isoforms. Soluble Amyloid A-protein caused no significant CA. A beta and beta 2M activated complement via the classical pathway. The modifying influence by amyloid-associated molecules on A beta-induced CA was also investigated, but neither serum amyloid P component nor heparan sulfate did significantly alter the A beta-induced CA. The results indicate that not only fibrillar A beta but also oligomers of, in particular, beta 2M from patients with dialysis-associated amyloidosis are capable of inducing CA at supra-physiological concentrations.
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Beta amyloid deposits and soluble B2M activate the classic complement cascade.
“both beta amyloid deposits and soluble B2M are known to activate the classic complement cascade77”
From Trisomy 21 causes changes in the circulating proteome indicative of chronic autoinflammation (2017) · cites this paper as [77]
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Metadata
- Authors
- Nybo, M., Nielsen, E. H., & Svehag, S.-E.
- Affiliations
- University of Southern Denmark (DK)
- Corresponding author
- Svehag, Sven-Erik
- ORCID
- Nybo, Mads
- Venue
- Amyloid
- Publisher
- Informa UK Limited
- Published
- 1999-01
- Volume
- 6
- Issue
- 4
- Pages
- 265-272
- ISSN
- 1350-6129 (ISSN-L)
- 1744-2818
- OpenAlex
- W2043355674
- Cited by
- 13
- References
- 38
- Citations by year
- 2022: 3 · 2017: 2
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Amyloid (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Prion Diseases and Protein Misfolding
- Keywords
- complement activation, amyloid-beta, beta2-microglobulin, Alzheimer's disease, amyloid fibrils, classical complement pathway, dialysis-related amyloidosis, serum amyloid P component, heparan sulfate, amyloid oligomers, amyloidogenesis
- MeSH terms
- Serum Amyloid P-Component, Serum Amyloid A Protein, Amyloidosis, beta 2-Microglobulin, Complement Activation, Hemolysis, Heparitin Sulfate, Heparan Sulfate, Humans, Kinetics, Microscopy, Electron, Peptide Fragments, Solubility, Spectrometry, Fluorescence, Amyloid beta-Peptides
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