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
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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.