Plasma levels of amyloid beta proteins A beta 1-40 and A beta 1-42(43) are elevated in Down's syndrome

To investigate the effect of the overexpression of beta-amyloid precursor protein (APP) on the production of two major amyloid beta protein (A beta) species, A beta 40 and A beta 42(43), we measured amounts of A beta 1-40 and A beta 1-42(43) in the plasma from 44 patients with Down's syndrome (DS) (age, 19-61 years) and 66 age-matched normal controls using enzyme-linked immunosorbent assays. Plasma concentrations of both A beta 1-40 and A beta 1-42(43) were increased about 3-fold and 2-fold, respectively, in DS patients compared with normal controls. Especially, the increases in plasma A beta 1-40 in DS patients were statistically higher than the 1.5-fold increase one might predict based on the gene dose of APP in DS. These findings showed that both A beta 1-40 and A beta 1-42(43) are increased in plasma in DS patients, the former more than the latter, suggesting that overexpression of APP and/or other genes may have different effects on the production of these two AP species in DS.