The in vitro neuronal toxicity of pentraxins associated with Alzheimer's disease brain lesions.
Serum amyloid P component (AP) and C-reactive protein (CRP) are normal serum components which belong to the pentraxin family of proteins. These proteins have been previously localized by immunohistochemical method to the brain lesions of Alzheimer's disease (AD). AP is a constant constituent of amyloid deposits including those found in AD. Both AP and CRP have been localized to AD neurofibrillary tangles. An indirect role for these proteins has been previously suggested in the etiology of AD. We studied the effects of serum AP and CRP on a human-derived neuronal cell line (hNT). In treated cell cultures, AP and CRP were detected immunohistochemically within hNT neurons, indicating cellular uptake of these proteins. Serum AP at the lowest serum physiological concentration (8 microgram/ml) showed a marked toxicity to hNT neurons. CRP also displayed toxicity to the hNT neurons but at a level compatible with inflammatory states (50 microgram/ml). These results suggest a more direct role for serum AP and CRP in the pathogenesis of AD.
Duong
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Indiana University School of Medicine, Terre Haute Center for Medical Education, Holmstedt Hall, Room 135, Terre Haute, IN 47809, USA. metpd@thcme.indstate.edu
Acton
P J
PJ
Johnson
R A
RA
D000209:Acute-Phase Proteins / Q000633:toxicity; D000544:Alzheimer Disease / Q000378:metabolism*; D000906:Antibodies; D001798:Blood Proteins / Q000494:pharmacology; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000032:analysis / Q000276:immunology / Q000633:toxicity*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016900:Neurofilament Proteins / Q000032:analysis / Q000276:immunology; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology*; D000683:Serum Amyloid P-Component / Q000032:analysis / Q000276:immunology / Q000633:toxicity*; D018243:Teratocarcinoma; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000209:Acute-Phase Proteins; D000906:Antibodies; D001798:Blood Proteins; D016900:Neurofilament Proteins; D000683:Serum Amyloid P-Component; C061195:neurofilament protein M; D002097:C-Reactive Protein; D007770:L-Lactate Dehydrogenase