Serum amyloid A (SAA)-induced remodeling of CSF-HDL.
Inflammation is a risk factor for Alzheimer's disease. Serum amyloid A (SAA) is an acute phase protein that dissociates apolipoprotein AI (apoAI) from plasma HDL. In cerebrospinal fluid (CSF), the SAA concentration is much higher in subjects with Alzheimer's disease than in controls. CSF-HDL is rich in apoE, which plays an important role as a ligand for lipoprotein receptors in the central nervous system (CNS). To clarify whether SAA dissociates apoE from CSF-HDL, we added recombinant SAA to CSF and determined the apoE distribution in the CSF using native two-dimensional gel electrophoresis. We found that SAA dissociated apoE from CSF-HDL in a dose-dependent manner. This effect was more evident in apoE4 carriers than in apoE3 or apoE2 carriers. After a 24-h incubation at 37 degrees C, SAA continuously dissociated apoE from CSF-HDL. Amyloid beta (Abeta) fragments (1-42) were bound to large CSF-HDL but not to apoE dissociated by SAA. In conclusion, SAA dissociates apoE from CSF-HDL. We postulate that inflammation in the CNS may impair Abeta clearance due to the loss of apoE from CSF-HDL.
Miida
Takashi
T
Division of Clinical Preventive Medicine, Department of Community Preventive Medicine, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata, Niigata 951-8510, Japan. miida@med.niigata-u.ac.jp
Yamada
Toshiyuki
T
Seino
Utako
U
Ito
Masayuki
M
Fueki
Yuriko
Y
Takahashi
Akihiro
A
Kosuge
Keiichiro
K
Soda
Satoshi
S
Hanyu
Osamu
O
Obayashi
Konen
K
Miyazaki
Osamu
O
Okada
Masahiko
M
D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood / Q000134:cerebrospinal fluid*; D010446:Peptide Fragments / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D010446:Peptide Fragments; D020033:Protein Isoforms; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; C075222:amyloid beta-protein (1-42)