C4b-binding protein in Alzheimer's disease: Binding to Abeta(1-42) and to dead cells.
Author
Summary, in English
In the Alzheimer's disease (AD) brain, binding of Clq within the Cl complex, the initiating molecule of the classical complement pathway, to apoptotic cells, DNA and amyloid-beta (Abeta), the major constituent of senile plaques, can initiate complement activation. However, the extent of activation is determined by the balance between activation and inhibition. Fluid-phase complement inhibitor C4b-binding protein (C4BP) was immunohistochemically detected in Abeta plaques and on apoptotic cells in AD brain. In vitro, C4BP bound apoptotic and necrotic but not viable brain cells (astrocytes, neurons and oligodendrocytes) and limited complement activation on dead brain cells. C4BP also bound Abeta(1-42) peptide directly, via the C4BP alpha-chain, and limited the extent of complement activation by Abeta. C4BP levels in cerebrospinal fluid (CSF) of dementia patients and controls were low compared to levels in plasma and correlated with CSF levels of other inflammation-related factors. In conclusion, C4BP binds to dead brain cells and Abeta peptide in vitro, is present in CSF and possibly protects against excessive complement activation in AD brains.
Department/s
- Chronic Inflammatory and Degenerative Diseases Research Unit
- Clinical Memory Research
- Pathology, Malmö
- Protein Chemistry, Malmö
Publishing year
2008
Language
English
Pages
3649-3660
Publication/Series
Molecular Immunology
Volume
45
Links
Document type
Journal article
Publisher
Pergamon Press Ltd.
Topic
- Immunology in the medical area
Status
Published
Research group
- Chronic Inflammatory and Degenerative Diseases Research Unit
- Clinical Memory Research
- Pathology, Malmö
- Protein Chemistry, Malmö
ISBN/ISSN/Other
- ISSN: 1872-9142