C4b-binding protein in Alzheimer's disease: Binding to Abeta(1-42) and to dead cells.
(2008) In Molecular Immunology 45. p.3649-3660- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1168769
- author
- Trouw, Leendert A ; Nielsen, Henrietta LU ; Minthon, Lennart LU ; Londos, Elisabet LU ; Landberg, Göran LU ; Veerhuis, Robert ; Janciauskiene, Sabina LU and Blom, Anna LU
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Immunology
- volume
- 45
- pages
- 3649 - 3660
- publisher
- Pergamon Press Ltd.
- external identifiers
-
- wos:000259473500018
- pmid:18556068
- scopus:46749123000
- pmid:18556068
- ISSN
- 1872-9142
- DOI
- 10.1016/j.molimm.2008.04.025
- language
- English
- LU publication?
- yes
- id
- 1c0cfef1-fc04-40c0-b791-256c264a8019 (old id 1168769)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/18556068?dopt=Abstract
- date added to LUP
- 2016-04-04 09:44:14
- date last changed
- 2022-04-23 22:05:46
@article{1c0cfef1-fc04-40c0-b791-256c264a8019, abstract = {{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.}}, author = {{Trouw, Leendert A and Nielsen, Henrietta and Minthon, Lennart and Londos, Elisabet and Landberg, Göran and Veerhuis, Robert and Janciauskiene, Sabina and Blom, Anna}}, issn = {{1872-9142}}, language = {{eng}}, pages = {{3649--3660}}, publisher = {{Pergamon Press Ltd.}}, series = {{Molecular Immunology}}, title = {{C4b-binding protein in Alzheimer's disease: Binding to Abeta(1-42) and to dead cells.}}, url = {{http://dx.doi.org/10.1016/j.molimm.2008.04.025}}, doi = {{10.1016/j.molimm.2008.04.025}}, volume = {{45}}, year = {{2008}}, }