Amyloid-beta peptides interact with plasma proteins and erythrocytes: Implications for their quantitation in plasma

Citation
Ym. Kuo et al., Amyloid-beta peptides interact with plasma proteins and erythrocytes: Implications for their quantitation in plasma, BIOC BIOP R, 268(3), 2000, pp. 750-756
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN journal
0006-291X → ACNP
Volume
268
Issue
3
Year of publication
2000
Pages
750 - 756
Database
ISI
SICI code
0006-291X(20000224)268:3<750:APIWPP>2.0.ZU;2-6
Abstract
Amyloid beta peptides are bound rapidly in the plasma complicating an accur ate assessment of their in vivo abundance by immunoassay procedures. The ex tent of A beta immunoassay interference was used to estimate the A beta bin ding capacity of purified plasma proteins, erythrocytes and whole plasma. H uman serum albumin bound A beta peptides rapidly with a 1:1 stoichiometry a nd at physiological concentrations was capable of binding over 95% of an in put of 5 ng/ml A beta. Purified alpha 2-macroglobulin was able to bind A be ta peptides and at physiological concentration bound 73% of 5 ng/ml of A be ta. Erythrocytes also sequestered the A beta peptides, showing a preference for binding A beta 1-42. Incubation of 5 ng/ml of A beta in plasma reveale d that about 30% of the peptides were still detectable by immunoassay, pres umably reflecting the binding of A beta peptides with albumin and other pla sma molecules. Thus, our studies reveal that both the soluble and formed el ements of the blood are capable of sequestering A beta peptides. To avoid u nderestimating plasma A beta values, we employed an improved column chromat ography method under denaturing conditions to liberate A beta from its asso ciations with plasma proteins. Quantification of A beta 40 and 42 levels in plasma from both normal and AD individuals after chromatography showed a l arge overlap between AD and control groups, despite the very large pool of A beta present in the AD brains. The potential origins of the plasma A beta pool are discussed. (C) 2000 Academic Press.