C4b-binding protein in Alzheimer's disease: binding to Abeta1-42 and to dead cells.
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 Abeta1-42 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 of Laboratory Medicine, Lund University, Malmö, Sweden.
Leendert A
LA
Trouw
Henrietta M
HM
Nielsen
Lennart
L
Minthon
Elisabet
E
Londos
Göran
G
Landberg
Robert
R
Veerhuis
Sabina
S
Janciauskiene
Anna M
AM
Blom
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D016923:Cell Death; D050716:Complement C4b-Binding Protein / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010446:Peptide Fragments / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding
D016229:Amyloid beta-Peptides; D050716:Complement C4b-Binding Protein; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)