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C4b-binding protein in Alzheimer's disease: Binding to Abeta(1-42) and to dead cells.

Trouw, Leendert A; Nielsen, Henrietta LU ; Minthon, Lennart LU ; Londos, Elisabet LU ; Landberg, Göran LU ; Veerhuis, Robert; Janciauskiene, Sabina LU and Blom, Anna LU (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)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Immunology
volume
45
pages
3649 - 3660
publisher
Pergamon
external identifiers
  • WOS:000259473500018
  • PMID:18556068
  • Scopus:46749123000
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
2008-07-02 15:20:34
date last changed
2016-10-23 04:33:12
@misc{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    = {ARRAY(0x8ebf0a8)},
  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},
  volume       = {45},
  year         = {2008},
}